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1.  Population-based incidence of Type 2 diabetes and its associated risk factors: results from a six-year cohort study in Iran 
BMC Public Health  2009;9:186.
Background
The Middle East is estimated to have the largest increase in prevalence of diabetes by 2030; yet there is lack of published data on the incidence of Type 2 diabetes in this region. This study aimed to estimate Type 2 diabetes incidence and its associated risk factors in an Iranian urban population.
Methods
Among 3307 non-diabetics ≥ 20 years (mean age 42 ± 13 years, 42% males), glucose tolerance test was performed at baseline in 1999–2001 and at two consecutive phases in 2001–2005 and 2005–2008. Diabetes and glucose tolerance status were defined according to the ADA 1997 criteria. Logistic regression was used to determine the independent variables associated with incident diabetes and their odds ratios (OR).
Results
After median follow-up of 6 years, 237 new cases of diabetes were ascertained corresponding to an age and sex standardized cumulative incidence of 6.4% (95%CI: 5.6–7.2) and incidence rate of 10.6 (9.2–12.1) per 1000 person years. Besides classical diabetes risk factors, female sex and low education level significantly increased risk of diabetes in age adjusted models. In full model, the independent predictors were age [OR, 95%CI: 1.2 (1.1–1.3)], family history of diabetes [1.8 (1.3–2.5)], body mass index ≥ 30 kg/m2 [2.3 (1.5–3.6)], abdominal obesity [1.9 (1.4–2.6)], high triglyceride [1.4 (1.1–1.9)], Isolated impaired fasting glucose (IFG) [7.4 (3.6–15.0)], Isolated impaired glucose tolerance (IGT) [5.9 (4.2–8.4)] and combined IFG and IGT [42.2 (23.8–74.9)].
Conclusion
More than 1% of the Iranian urban population older than 20 years develops Type 2 diabetes each year. Combination of IFG and IGT was the strongest predictor of incident diabetes among the modifiable risk factors.
doi:10.1186/1471-2458-9-186
PMCID: PMC2708154  PMID: 19531260
2.  The overall health and risk factor profile of Australian Aboriginal and Torres Strait Islander participants from the 45 and up study 
BMC Public Health  2013;13:661.
Background
Despite large disparities in health outcomes between Aboriginal and non-Aboriginal Australians, detailed evidence on the health and lifestyle characteristics of older Aboriginal Australians is lacking. The aim of this study is to quantify socio-demographic and health risk factors and mental and physical health status among Aboriginal participants from the 45 and Up Study and to compare these with non-Aboriginal participants from the study.
Methods
The 45 and Up Study is a large-scale study of individuals aged 45 years and older from the general population of New South Wales, Australia responding to a baseline questionnaire distributed from 2006–2008. Odds ratios (OR) and 95% confidence intervals (CI) of self-reported responses from the baseline questionnaire for Aboriginal versus non-Aboriginal participants relating to socio-demographic factors, health risk factors, current and past medical and surgical history, physical disability, functional health limitations and levels of current psychological distress were calculated using unconditional logistic regression, with adjustments for age and sex.
Results
Overall, 1939 of 266,661 45 and Up Study participants examined in this study identified as Aboriginal and/or Torres Strait Islander (0.7%). Compared to non-Aboriginal participants, Aboriginal participants were significantly more likely to be: younger (mean age 58 versus 63 years); without formal educational qualifications (age- and sex- adjusted OR = 6.2, 95% CI 5.3-7.3); of unemployed (3.7, 2.9-4.6) or disabled (4.6, 3.9-5.3) work status; and with a household income < $20,000/year versus ≥ $70,000/year (5.8, 5.0-6.9). Following additional adjustment for income and education, Aboriginal participants were significantly more likely than non-Aboriginal participants to: be current smokers (2.4, 2.0-2.8), be obese (2.1, 1.8-2.5), have ever been diagnosed with certain medical conditions (especially: diabetes [2.1, 1.8-2.4]; depression [1.6, 1.4-1.8] and stroke [1.8, 1.4-2.3]), have care-giving responsibilities (1.8, 1.5-2.2); have a major physical disability (2.6, 2.2-3.1); have severe physical functional limitation (2.9, 2.4-3.4) and have very high levels of psychological distress (2.4, 2.0-3.0).
Conclusions
Aboriginal participants from the 45 and Up Study experience greater levels of disadvantage and have greater health needs (including physical disability and psychological distress) compared to non-Aboriginal participants. The study highlights the need to address the social determinants of health in Australia and to provide appropriate mental health services and disability support for older Aboriginal people.
doi:10.1186/1471-2458-13-661
PMCID: PMC3717143  PMID: 23866062
Aboriginal Australians; Torres Strait Islanders; 45 and Up study
3.  Survival of the fattest: unexpected findings about hyperglycaemia and obesity in a population based study of 75-year-olds 
BMJ Open  2011;1(1):e000012.
Objective
To study the relationship between body mass index (BMI) and mortality among 75-year-olds with and without diabetes mellitus type 2 (DM) or impaired fasting glucose (IFG).
Design
Prospective population-based cohort study with a 10-year follow-up.
Participants
A random sample of 618 of the 1100 inhabitants born in 1922 and living in the city of Västerås in 1997 were invited to participate in a cardiovascular health survey; 70% of those invited agreed to participate (432 individuals: 210 men, 222 women).
Outcome measures
All-cause and cardiovascular mortality.
Results
163 of 432 (38%) participants died during the 10-year follow-up period. The prevalence of DM or IFG was 41% (35% among survivors, 48% among non-survivors). The prevalence of obesity/overweight/normal weight/underweight according to WHO definitions was 12/45/42/1% (14/43/42/1% among survivors, 9/47/42/2% among non-survivors). The hazard rate for death decreased by 10% for every kg/m2 increase in BMI in individuals with DM/IFG (HR 0.91, 95% CI 0.86 to 0.97; p=0.003). After adjustment for sex, current smoking, diagnosed hypertension, diagnosed angina pectoris, previous myocardial infarction and previous stroke/transient ischaemic attack, the corresponding decrease in mortality was 9% (HR 0.92, 95% CI 0.86 to 0.99; p=0.017). These findings remained after exclusion of individuals with BMI<20 or those who died within 2-year follow-up. In individuals without DM/IFG, BMI had no effect on mortality (HR 1.01, 95% CI 0.95 to 1.07; p=0.811). The HR for BMI differed significantly between individuals with and without DM/IFG (p interaction=0.025). The increased all-cause mortality in individuals with DM/IFG in combination with lower BMI was driven by cardiovascular death.
Conclusion
High all-cause and cardiovascular mortality was associated with lower BMI in 75-year-olds with DM/IFG but not in those without DM/IFG. Further studies on the combined effect of obesity/overweight and DM/IFG are needed in order to assess the appropriateness of current guideline recommendations for weight reduction in older people with DM/IFG.
Article summary
Article focus
To explore the combined effect of hyperglycaemia and body mass index (BMI) on all-cause and cardiovascular mortality in the elderly.
Key messages
There was a significant inverse relationship in 75-year-olds with type 2 diabetes mellitus (DM) or impaired fasting glucose (IFG) between BMI and rate of all-cause and cardiovascular mortality.
An obesity paradox or reverse epidemiology was found in 75-year-olds with DM or IFG.
Further studies on the combined effect of obesity/overweight and DM/IFG are needed in order to assess current guidelines for weight reduction in older people with DM/IFG.
Strengths and limitations of this study
Restricting our investigation to one age group enabled us to omit age as a confounding factor, allowing meaningful estimation of the relationship between all-cause and cardiovascular mortality and BMI in individuals with and without hyperglycaemia, despite the relatively small number of study participants. Furthermore, because of the high participation rate, the participants are more representative of the population in a defined geographical area than described in most other studies on this topic. These advantages are, however, offset by difficulty in generalising our findings to those in other age groups and from other geographical areas. Nevertheless, it seems likely that our results are applicable to Northern Europeans and white North Americans in their seventies.
A further limitation of the study is the fact that mortality among invited individuals who did not participate in the study (30%) was considerably higher than among those who participated (70%), mainly reflecting a higher prevalence of diseases under treatment among non-participants.
doi:10.1136/bmjopen-2010-000012
PMCID: PMC3191391  PMID: 22021724
BMI; cardiovascular diseases; elderly; fasting glucose; mortality; obesity paradox; epidemiology; Computers; meta-analysis; statistics; BMJ open
4.  Does Elevated Plasma Triglyceride Level Independently Predict Impaired Fasting Glucose? 
Diabetes Care  2013;36(2):342-347.
OBJECTIVE
Elevated plasma triglycerides (TGs) have been included in diabetes risk prediction models. This study examined whether elevated TGs predict risk for impaired fasting glucose (IFG).
RESEARCH DESIGN AND METHODS
This study used the baseline and longitudinal follow-up data from the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included non-Hispanic whites, African Americans, Hispanics, and Chinese Americans 45–84 years of age who had fasting glucose <100 mg/dL at baseline and who did not have clinically evident cardiovascular disease or diabetes. Cox proportional regression models were used to examine the association of elevated TGs with incidence of IFG adjusting for central obesity, low HDL cholesterol, elevated blood pressure, baseline fasting glucose, and BMI. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of elevated TGs in predicting IFG were calculated.
RESULTS
The incidence rate of developing IFG was 59.1 per 1,000 person-years during the median 4.75 years of follow-up. African Americans and Hispanics had a higher incidence rate of IFG compared with non-Hispanic whites among people with normal TG concentrations. Elevated TGs (>150 mg/dL) at baseline were independently associated with the incidence of IFG with an adjusted hazard ratio of 1.19 (95% CI 1.04–1.37). However, its predictive value for identifying people at risk for IFG was poor, with <57% AUC. Interactions of elevated TGs with race/ethnicity in predicting IFG were not statistically significant.
CONCLUSIONS
Elevated TGs were moderately associated with risk for IFG, and it was a poor risk prediction tool for IFG.
doi:10.2337/dc12-0355
PMCID: PMC3554324  PMID: 23033247
5.  Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation 
Diabetes Care  2013;36(4):992-997.
OBJECTIVE
To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.
RESEARCH DESIGN AND METHODS
We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m2 (age 46–65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).
RESULTS
BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m2.7 in men) was 3.5 in IFG participants (95% CI 0.68–17.76; P = NS) and 9.76 (2.03–46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.
CONCLUSIONS
Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).
doi:10.2337/dc12-1501
PMCID: PMC3609517  PMID: 23223343
6.  High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study 
BMC Public Health  2008;8:176.
Background
To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years.
Methods
The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes.
Results
The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4).
Conclusion
In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.
doi:10.1186/1471-2458-8-176
PMCID: PMC2413226  PMID: 18501007
7.  Predictors of Progression From Impaired Glucose Tolerance to NIDDM 
Diabetes  1997;46(4):701-710.
Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.
PMCID: PMC2517225  PMID: 9075814
8.  Impaired Glucose Tolerance and Obesity as Effect Modifiers of Ethnic Disparities of the Progression to Diabetes 
Diabetes Care  2012;35(12):2548-2552.
OBJECTIVE
The Diabetes Prevention Program (DPP) reported no racial/ethnic differences in the incidence of diabetes in individuals with impaired glucose tolerance (IGT). Therefore, it has been hypothesized that factors associated with racial/ethnic disparities act prior to the development of IGT. Because impaired fasting glucose (IFG) and obesity were also very prevalent in the DPP, we examined IGT, IFG, and obesity as effect modifiers of ethnic disparities in the San Antonio Heart Study.
RESEARCH DESIGN AND METHODS
Participants were 3,015 Mexican Americans and non-Hispanic whites aged 25–64 years. The median follow-up period was 7.8 years. IGT, IFG, and diabetes were defined by the 2003 American Diabetes Association criteria, and obesity was defined as BMI ≥30 kg/m2.
RESULTS
Mexican Americans had an excess risk of incident IGT (odds ratio 1.48 [95% CI 1.16–1.89]) and incident IFG (1.71 [1.31–2.23]) compared with non-Hispanic whites. Mexican Americans also had a higher incidence of diabetes among individuals who had normal 2-h glucose (2.20 [1.48–3.29]) and IGT (1.72 [1.08–2.74]) at baseline. There was an interaction of obesity on the relationship between ethnicity and progression to IGT or diabetes (P = 0.034), with Mexican Americans having a greater risk among the nonobese (1.73 [1.36–2.21]) and a comparable risk among the obese (1.08 [0.75–1.56]).
CONCLUSIONS
Ethnic differences can be detected at both the early and later stages of the diabetes disease process. However, non-Hispanic whites lose much of the ethnic advantage once they have developed obesity.
doi:10.2337/dc11-1902
PMCID: PMC3507579  PMID: 22923668
9.  The Relative Associations of β-Cell Function and Insulin Sensitivity with Glycemic Status and Incident Glycemic Progression in Migrant Asian Indians in the United States: the MASALA study 
Journal of diabetes and its complications  2013;28(1):10.1016/j.jdiacomp.2013.10.002.
AIMS
We assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States.
METHODS
A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia.
RESULTS
Mean age was 57±8 years and BMI 26.1±4.6 kg/m2. Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-year) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β(OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression.
CONCLUSIONS
The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia.
doi:10.1016/j.jdiacomp.2013.10.002
PMCID: PMC3877179  PMID: 24211090
type 2 diabetes mellitus; Asian Indians; insulin sensitivity; β-cell dysfunction; ethnicity; incidence; impaired glucose tolerance; impaired fasting glucose
10.  Recent epidemiologic trends of diabetes mellitus among status Aboriginal adults 
Background:
Little is known about longitudinal trends in diabetes mellitus among Aboriginal people in Canada. We compared the incidence and prevalence of diabetes, and its impact on mortality, among status Aboriginal adults and adults in the general population between 1995 and 2007.
Methods:
We examined de-identified data from Alberta Health and Wellness administrative databases for status Aboriginal people (First Nations and Inuit people with treaty status) and members of the general public aged 20 years and older who received a diagnosis of diabetes mellitus from Apr. 1, 1995, to Mar. 31, 2007. We calculated the incidence and prevalence of diabetes and mortality rate ratios by sex and ethnicity in 2007. We examined the average relative changes per year for longitudinal trends.
Results:
The average relative change per year in the prevalence of diabetes showed a smaller increase over time in the Aboriginal population than in the general population (2.39 v. 4.09, p < 0.001). A similar finding was observed for the incidence of diabetes. In the Aboriginal population, we found that the increase in the average relative change per year was greater among men than among women (3.13 v. 1.88 for prevalence, p < 0.001; 2.60 v. 0.02 for incidence, p = 0.001). Mortality among people with diabetes decreased over time to a similar extent in both populations. Among people without diabetes, mortality decreased in the general population but was unchanged in the Aboriginal population (−1.92 v. 0.11, p = 0.04). Overall, mortality was higher in the Aboriginal population than in the general population regardless of diabetes status.
Interpretation:
The increases in the incidence and prevalence of diabetes over the study period appeared to be slower in the status Aboriginal population than in the general population in Alberta, although the overall rates were higher in the Aboriginal population. Mortality decreased among people with diabetes in both populations but was higher overall in the Aboriginal population regardless of diabetes status.
doi:10.1503/cmaj.101882
PMCID: PMC3168663  PMID: 21788417
11.  Appropriateness of current thresholds for obesity-related measures among Aboriginal people 
Background
Despite the high prevalence of obesity and diabetes in the Canadian Aboriginal population, it is unknown whether the current thresholds for body mass index and waist circumference derived from white populations are appropriate for Aboriginal people. We compared the risk of cardiovascular disease among Canadian Aboriginal and European populations using the current thresholds for body mass index and waist circumference.
Methods
Healthy Aboriginal (n = 195) and European (n = 201) participants (matched for sex and body mass index range) were assessed for demographic characteristics, lifestyle factors, total and central adiposity and risk factors for cardiovascular disease. Among Aboriginal and European participants, we compared the relation between body mass index and each of the following 3 factors: percent body fat, central adiposity and cardiovascular disease risk factors. We also compared the relation between waist circumference and the same 3 factors.
Results
The use of body mass index underestimated percent body fat by 1.3% among Aboriginal participants compared with European participants (p = 0.025). The use of waist circumference overestimated abdominal adipose tissue by 26.7 cm2 among Aboriginal participants compared with European participants (p = 0.007). However, there was no difference in how waist circumference estimated subcutaneous abdominal and visceral adipose tissue among the 2 groups. At the same body mass index and waist circumference, we observed no differences in the majority of cardiovascular disease risk factors among Aboriginal and European participants. The prevalence of dyslipidemia, hypertension, impaired fasting glucose and metabolic syndrome was similar among participants in the 2 groups after adjustment for body mass index, waist circumference, age and sex.
Interpretation
We found no difference in the relation between body mass index and risk of cardiovascular disease between men and women of Aboriginal and European descent. We also found no difference between waist circumference and cardiovascular disease risk among these groups. These data support the use of current anthropometric thresholds in the Canadian Aboriginal population.
doi:10.1503/cmaj.070302
PMCID: PMC2096496  PMID: 18056598
12.  Evidence of Reduced β-Cell Function in Asian Indians With Mild Dysglycemia 
Diabetes Care  2013;36(9):2772-2778.
OBJECTIVE
To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI.
RESEARCH DESIGN AND METHODS
One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δinsulin0–30/Δglucose0–30] × [1/fasting insulin]).
RESULTS
Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m2 (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23–0.55; iIGT: OR, 0.37; 95% CI, 0.24–0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23–2.33; iIGT: OR, 1.53; 95% CI, 1.11–2.11).
CONCLUSIONS
Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.
doi:10.2337/dc12-2290
PMCID: PMC3747932  PMID: 23596180
13.  Inequalities in ventilation tube insertion procedures between Aboriginal and non-Aboriginal children in New South Wales, Australia: a data linkage study 
BMJ Open  2013;3(11):e003807.
Objectives
Australian Aboriginal children experience earlier, more frequent and more severe otitis media, particularly in remote communities, than non-Aboriginal children. Insertion of ventilation tubes is the main surgical procedure for otitis media. Our aim was to quantify inequalities in ventilation tube insertion (VTI) procedures between Australian Aboriginal and non-Aboriginal children, and to explore the influence of birth characteristics, socioeconomic background and geographical remoteness on this inequality.
Design
Retrospective cohort study using linked hospital and mortality data from July 2000 to December 2008.
Setting and participants
A whole-of-population cohort of 653 550 children (16 831 Aboriginal and 636 719 non-Aboriginal) born in a New South Wales hospital between 1 July 2000 and 31 December 2007 was included in the analysis.
Outcome measure
First VTI procedure.
Results
VTI rates were lower in Aboriginal compared with non-Aboriginal children (incidence rate (IR), 4.3/1000 person-years; 95% CI 3.8 to 4.8 vs IR 5.8/1000 person-years; 95% CI 5.7 to 5.8). Overall, Aboriginal children were 28% less likely than non-Aboriginal children to have ventilation tubes inserted (age-adjusted and sex-adjusted rate ratios (RRs) 0.72; 95% CI 0.64 to 0.80). After adjusting additionally for geographical remoteness, Aboriginal children were 19% less likely to have ventilation tubes inserted (age-adjusted and sex-adjusted RR 0.81; 95% CI 0.73 to 0.91). After adjusting separately for private patient/health insurance status and area socioeconomic status, there was no significant difference (age-adjusted and sex-adjusted RR 0.96; 95% CI 0.86 to 1.08 and RR 0.93; 95% CI 0.83 to 1.04, respectively). In the fully adjusted model, there were no significant differences in VTI rates between Aboriginal and non-Aboriginal children (RR 1.06; 95% CI 0.94 to 1.19).
Conclusions
Despite a much higher prevalence of otitis media, Aboriginal children were less likely to receive VTI procedures than their non-Aboriginal counterparts; this inequality was largely explained by differences in socioeconomic status and geographical remoteness.
doi:10.1136/bmjopen-2013-003807
PMCID: PMC3845074  PMID: 24285631
Epidemiology; Public Health
14.  Efficacy of Primary Prevention Interventions When Fasting and Postglucose Dysglycemia Coexist 
Diabetes Care  2010;33(10):2164-2168.
OBJECTIVE
Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have different pathophysiological abnormalities, and their combination may influence the effectiveness of the primary prevention tools. The hypothesis was tested in this analysis, which was done in a pooled sample of two Indian Diabetes Prevention Programmes (IDPP-1 and IDPP-2).
RESEARCH DESIGN AND METHODS
Researchers analyzed and followed up on the details of 845 of the 869 IGT subjects in the two studies for 3 years. Incidence of diabetes and reversal to normoglycemia (normal glucose tolerance [NGT]) were assessed in group 1 with baseline isolated IGT (iIGT) (n = 667) and in group 2 with IGT + IFG (n = 178). The proportion developing diabetes in the groups were analyzed in the control arm with standard advice (IDPP-1) (n = 125), lifestyle modification (LSM) (297 from both), metformin (n = 125, IDPP-1), and LSM + metformin (n = 121, IDPP-1) and LSM + pioglitazone (n = 298, IDPP-2). Cox regression analysis was used to assess the influence of IGT + IFG versus iIGT on the effectiveness of the interventions.
RESULTS
Group 2 had a higher proportion developing diabetes in 3 years (56.2 vs. 33.6% in group 1, P = 0.000) and a lower rate of reversal to NGT (18 vs. 32.1%, P = 0.000). Cox regression analysis showed that effectiveness of intervention was not different in the presence of fasting and postglucose glycemia after adjusting for confounding variables.
CONCLUSIONS
The effectiveness of primary prevention strategies appears to be similar in subjects with iIGT or with combined IGT + IFG. However, the possibility remains that a larger study might show that the effectiveness is lower in those with the combined abnormality.
doi:10.2337/dc09-1150
PMCID: PMC2945153  PMID: 20519663
15.  Incidence and causes of end-stage renal disease among Aboriginal children and young adults 
Background:
Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described.
Methods:
We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years.
Results:
Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age < 22 yr, v. white people) were 1.82 (95% confidence interval [CI] 1.40–2.38) for boys and 3.24 (95% CI 2.60–4.05) for girls. Compared with white people, congenital diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36–0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55–3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older.
Interpretation:
The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.
doi:10.1503/cmaj.120427
PMCID: PMC3470642  PMID: 22927509
16.  Death and renal transplantation among Aboriginal people undergoing dialysis 
Background
Despite the increase in the number of Aboriginal people with end-stage renal disease around the world, little is known about their health outcomes when undergoing renal replacement therapy. We evaluated differences in survival and rate of renal transplantation among Aboriginal and white patients after initiation of dialysis.
Methods
Adult patients who were Aboriginal or white and who commenced dialysis in Alberta, Saskatchewan or Manitoba between Jan. 1, 1990, and Dec. 31, 2000, were recruited for the study and were followed until death, transplantation, loss to follow-up or the end of the study (Dec. 31, 2001). We used Cox proportional hazards models to examine the effect of race on patient survival and likelihood of transplant, with adjustment for potential confounders.
Results
Of the 4333 adults who commenced dialysis during the study period, 15.8% were Aboriginal and 72.4% were white. Unadjusted rates of death per 1000 patient-years during the study period were 158 (95% confidence interval [CI] 144–176) for Aboriginal patients and 146 (95% CI 139–153) for white patients. When follow-up was censored at the time of transplantation, the age-adjusted risk of death after initiation of dialysis was significantly higher among Aboriginal patients than among white patients (hazard ratio [HR] 1.15, 95% CI 1.02–1.30). The greater risk of death associated with Aboriginal race was no longer observed after adjustment for diabetes mellitus and other comorbid conditions (adjusted HR 0.89, 95% CI 0.77–1.02) and did not appear to be associated with socioeconomic status. During the study period, unadjusted transplantation rates per 1000 patient-years were 62 (95% CI 52–75) for Aboriginal patients and 133 (95% CI 125–142) for white patients. Aboriginal patients were significantly less likely to receive a renal transplant after commencing dialysis, even after adjustment for potential confounders (HR 0.43, 95% CI 0.35–0.53). In an additional analysis that included follow-up after transplantation for those who received renal allografts, the age-adjusted risk of death associated with Aboriginal race (HR 1.36, 95% CI 1.21–1.52) was higher than when follow-up after transplantation was not considered, perhaps because of the lower rate of transplantation among Aboriginals.
Interpretation
Survival among dialysis patients was similar for Aboriginal and white patients after adjustment for comorbidity. However, despite universal access to health care, Aboriginal people had a significantly lower rate of renal transplantation, which might have adversely affected their survival when receiving renal replacement therapy.
doi:10.1503/cmaj.1031859
PMCID: PMC516192  PMID: 15367459
17.  Is There a Link Between Components of Health-Related Functioning and Incident Impaired Glucose Metabolism and Type 2 Diabetes? 
Diabetes Care  2009;33(4):757-762.
OBJECTIVE
To determine the longitudinal association of components of health-related functioning (HRF) with incident impaired glucose metabolism and type 2 diabetes.
RESEARCH DESIGN AND METHODS
The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged ≥25 years from 42 randomly selected areas of Australia. Diabetes status was defined using the World Health Organization criteria, and HRF was assessed using the SF-36 questionnaire in 1999–2000 and 2004–2005.
RESULTS
Incident impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes were associated with increased bodily pain at baseline compared with those with normal glucose tolerance (NGT) (IFG P = 0.005, IGT P < 0.004, and newly diagnosed type 2 diabetes P = 0.005), after adjustment. In addition, those with incident IGT and newly diagnosed type 2 diabetes had significantly reduced physical functioning, general health, mental health, and vitality at baseline compared with those with NGT. After we controlled for factors associated with incident diabetes, those in the lowest quartile of the physical component summary scale at baseline had at least a 50% higher risk of progression to impaired glucose metabolism and diabetes 5 years later.
CONCLUSIONS
These findings show that incident IFG, IGT, and newly diagnosed type 2 diabetes are associated with reduced HRF independent of cardiovascular disease and that this is evident before the onset of these conditions. If future health promotion campaigns are to effectively target those at high risk of developing diabetes, an understanding of the process of declining health before onset of the disease is essential.
doi:10.2337/dc09-1107
PMCID: PMC2845023  PMID: 20007943
18.  Association between Markers of Fatty Liver Disease and Impaired Glucose Regulation in Men and Women from the General Population: The KORA-F4-Study 
PLoS ONE  2011;6(8):e22932.
Objective
To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population.
Methods
The study was based on 3009 subjects (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI).
Results
229 participants (7.6%) reported known diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%) were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47–2.09], in IFG OR = 1.79 [1.50–2.13], GPT in diabetic persons OR = 1.51, [1.30–1.74], in NDD OR = 1.77 [1.52–2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13–14.00], 6.70 [3.74–12.01] for combined IFG and IGT and 4.78 [3.47–6.59] for known diabetes respectively.
Conclusions
Elevated GGT and GPT–values as well as estimates of fatty liver disease are significantly associated with pre-diabetes and diabetes and thus very useful first indicators of a disturbed glucose metabolism.
doi:10.1371/journal.pone.0022932
PMCID: PMC3151286  PMID: 21850244
19.  Impaired Fasting Glucose and Risk of Cardiovascular Disease in Korean Men and Women 
Diabetes Care  2013;36(2):328-335.
OBJECTIVE
The relationship between impaired fasting glucose (IFG) and risk of cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely according to sex and ethnicity. We evaluated the relationship between IFG and CVD or IHD among Korean men and women.
RESEARCH DESIGN AND METHODS
A total of 408,022 individuals who underwent voluntary private health examinations in 17 centers in South Korea were followed for 10 years. Data regarding CVD or IHD events were obtained from the Korean National Health Insurance database. IFG was categorized as grade 1 (fasting glucose 100–109 mg/dL) or grade 2 (110–125 mg/dL).
RESULTS
Incidence rates of CVD (per 100,000 person-years) were 2,203 for diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13–1.20) for grade 1 IFG, 1.30 (1.24–1.35) for grade 2 IFG, and 1.81 (1.75–1.86) for diabetes. The increased risk for women was similar to that of men. Age-adjusted HRs for IHD and ischemic stroke were also significantly increased for men and women with IFG and diabetes. After multivariate adjustment of conventional risk factors (hypertension, dyslipidemia, smoking, obesity, and family history of CVD), the overall risk of CVD was greatly attenuated in all categories. However, the HRs for IHD and ischemic stroke remained significantly increased in men for grade 2 IFG but not in women.
CONCLUSIONS
In Korea, grade 2 IFG is associated with increased risk of IHD and ischemic stroke, independent of other conventional risk factors, in men but not in women.
doi:10.2337/dc12-0587
PMCID: PMC3554281  PMID: 23002083
20.  Lifestyle Intervention for Prevention of Type 2 Diabetes in Primary Health Care 
Diabetes Care  2010;33(10):2146-2151.
OBJECTIVE
To investigate 1-year outcomes of a national diabetes prevention program in Finland.
RESEARCH DESIGN AND METHODS
Altogether 10,149 individuals at high risk for diabetes were identified with the Finnish Diabetes Risk Score (FINDRISC; scoring ≥15 points), by a history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), cardiovascular disease, or gestational diabetes mellitus in 400 primary health care centers. One-year follow-up data were available for 2,798 participants who were nondiabetic at baseline (919 men and 1,879 women, aged 56.0 ± 9.9 and 54.0 ± 10.7 years [mean ± SD] with BMI 30.9 ± 4.6 and 31.6 ± 5.4 kg/m2).
RESULTS
The incidence of diabetes was 2.0 and 1.2% in men and women with normal glucose tolerance at baseline, 13.5 and 7.4% in those with IFG, and 16.1 and 11.3% in those with IGT, respectively. Altogether 17.5% of the subjects lost ≥5% weight with no sex difference. The relative risk of diabetes was 0.31 (95% CI 0.16–0.59) in the group who lost ≥5% weight, 0.72 (0.46–1.13) in the group who lost 2.5–4.9% weight, and 1.10 (0.77–1.58) in the group who gained ≥2.5% compared with the group who maintained weight.
CONCLUSIONS
The FIN-D2D was the first national effort to implement the prevention of diabetes in a primary health care setting. Methods for recruiting high-risk subjects were simple and easy to use. Moderate weight loss in this very high-risk group was especially effective in reducing risk of diabetes among those participating in the program.
doi:10.2337/dc10-0410
PMCID: PMC2945150  PMID: 20664020
21.  Long-Term Risk of Incident Type 2 Diabetes and Measures of Overall and Regional Obesity: The EPIC-InterAct Case-Cohort Study 
PLoS Medicine  2012;9(6):e1001230.
A collaborative re-analysis of data from the InterAct case-control study conducted by Claudia Langenberg and colleagues has established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index.
Background
Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).
Methods and Findings
The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5–22.4 kg/m2) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m2) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50–103 per 1,000 person-years in men and 28–74 per 1,000 person-years in women).
Conclusions
WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone that the pancreas releases after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. The long-term complications of diabetes, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
A high body mass index (BMI, a measure of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is a strong predictor of type 2 diabetes. Although the risk of diabetes is greatest in obese people (who have a BMI of greater than 30 kg/m2), many of the people who develop diabetes are overweight—they have a BMI of 25–30 kg/m2. Healthy eating and exercise reduce the incidence of diabetes in high-risk individuals, but it is difficult and expensive to provide all overweight and obese people with individual lifestyle advice. Ideally, a way is needed to distinguish between people with high and low risk of developing diabetes at different levels of BMI. Waist circumference is a measure of fat distribution that has the potential to quantify diabetes risk among people with different BMIs because it estimates the amount of fat around the abdominal organs, which also predicts diabetes development. In this case-cohort study, the researchers use data from the InterAct study (which is investigating how genetics and lifestyle interact to affect diabetes risk) to estimate the long-term risk of type 2 diabetes associated with BMI and waist circumference. A case-cohort study measures exposure to potential risk factors in a group (cohort) of people and compares the occurrence of these risk factors in people who later develop the disease and in a randomly chosen subcohort.
What Did the Researchers Do and Find?
The researchers estimated the association of BMI and waist circumference with type 2 diabetes from baseline measurements of the weight, height, and waist circumference of 12,403 people who subsequently developed type 2 diabetes and a subcohort of 16,154 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC). Both risk factors were independently associated with type 2 diabetes risk, but waist circumference was a stronger risk factor in women than in men. Obese men (BMI greater than 35 kg/m2) with a high waist circumference (greater than 102 cm) were 22 times more likely to develop diabetes than men with a low normal weight (BMI 18.5–22.4 kg/m2) and a low waist circumference (less than 94 cm); obese women with a waist circumference of more than 88 cm were 31.8 times more likely to develop type 2 diabetes than women with a low normal weight and waist circumference (less than 80 cm). Importantly, among overweight people, waist circumference measurements identified a subgroup of overweight people (those with a high waist circumference) whose 10-year cumulative incidence of type 2 diabetes was similar to that of obese people.
What Do These Findings Mean?
These findings indicate that, among people of European descent, waist circumference is independently and strongly associated with type 2 diabetes, particularly among women. Additional studies are needed to confirm this association in other ethnic groups. Targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualized lifestyle advice.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001230.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public, including detailed information on diabetes prevention (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (including some information in Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes, about the prevention of type 2 diabetes, and about obesity; it also includes peoples stories about diabetes and about obesity
The charity Diabetes UK also provides detailed information for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes
More information on the InterAct study is available
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)
doi:10.1371/journal.pmed.1001230
PMCID: PMC3367997  PMID: 22679397
22.  Patterns of Obesity Development before the Diagnosis of Type 2 Diabetes: The Whitehall II Cohort Study 
PLoS Medicine  2014;11(2):e1001602.
Examining patterns of change in body mass index (BMI) and other cardiometabolic risk factors in individuals during the years before they were diagnosed with diabetes, Kristine Færch and colleagues report that few of them experienced dramatic BMI changes.
Please see later in the article for the Editors' Summary
Background
Patients with type 2 diabetes vary greatly with respect to degree of obesity at time of diagnosis. To address the heterogeneity of type 2 diabetes, we characterised patterns of change in body mass index (BMI) and other cardiometabolic risk factors before type 2 diabetes diagnosis.
Methods and Findings
We studied 6,705 participants from the Whitehall II study, an observational prospective cohort study of civil servants based in London. White men and women, initially free of diabetes, were followed with 5-yearly clinical examinations from 1991–2009 for a median of 14.1 years (interquartile range [IQR]: 8.7–16.2 years). Type 2 diabetes developed in 645 (1,209 person-examinations) and 6,060 remained free of diabetes during follow-up (14,060 person-examinations). Latent class trajectory analysis of incident diabetes cases was used to identify patterns of pre-disease BMI. Associated trajectories of cardiometabolic risk factors were studied using adjusted mixed-effects models. Three patterns of BMI changes were identified. Most participants belonged to the “stable overweight” group (n = 604, 94%) with a relatively constant BMI level within the overweight category throughout follow-up. They experienced slightly worsening of beta cell function and insulin sensitivity from 5 years prior to diagnosis. A small group of “progressive weight gainers” (n = 15) exhibited a pattern of consistent weight gain before diagnosis. Linear increases in blood pressure and an exponential increase in insulin resistance a few years before diagnosis accompanied the weight gain. The “persistently obese” (n = 26) were severely obese throughout the whole 18 years before diabetes diagnosis. They experienced an initial beta cell compensation followed by loss of beta cell function, whereas insulin sensitivity was relatively stable. Since the generalizability of these findings is limited, the results need confirmation in other study populations.
Conclusions
Three patterns of obesity changes prior to diabetes diagnosis were accompanied by distinct trajectories of insulin resistance and other cardiometabolic risk factors in a white, British population. While these results should be verified independently, the great majority of patients had modest weight gain prior to diagnosis. These results suggest that strategies focusing on small weight reductions for the entire population may be more beneficial than predominantly focusing on weight loss for high-risk individuals.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, a metabolic disorder characterized by high amounts of glucose (sugar) in the blood. Blood sugar levels are normally controlled by insulin, a hormone released by the pancreas after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes) blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes, which was previously called adult-onset diabetes, can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. Long-term complications, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes. The number of people with diabetes is expected to increase dramatically over the next decades, coinciding with rising obesity rates in many countries. To better understand diabetes development, to identify people at risk, and to find ways to prevent the disease are urgent public health goals.
Why Was This Study Done?
It is known that people who are overweight or obese have a higher risk of developing diabetes. Because of this association, a common assumption is that people who experienced recent weight gain are more likely to be diagnosed with diabetes. In this prospective cohort study (an investigation that records the baseline characteristics of a group of people and then follows them to see who develops specific conditions), the researchers tested the hypothesis that substantial weight gain precedes a diagnosis of diabetes and explored more generally the patterns of body weight and composition in the years before people develop diabetes. They then examined whether changes in body weight corresponded with changes in other risk factors for diabetes (such as insulin resistance), lipid profiles and blood pressure.
What Did the Researchers Do and Find?
The researchers studied participants from the Whitehall II study, a prospective cohort study initiated in 1985 to investigate the socioeconomic inequalities in disease. Whitehall II enrolled more than 10,000 London-based government employees. Participants underwent regular health checks during which their weight and height were measured, blood tests were done, and they filled out questionnaires for other relevant information. From 1991 onwards, participants were tested every five years for diabetes. The 6,705 participants included in this study were initially free of diabetes, and most of them were followed for at least 14 years. During the follow-up, 645 participants developed diabetes, while 6,060 remained free of the disease.
The researchers used a statistical tool called “latent class trajectory analysis” to study patterns of changes in body mass index (BMI) in the years before people developed diabetes. BMI is a measure of human obesity based on a person's weight and height. Latent class trajectory analysis is an unbiased way to subdivide a number of people into groups that differ based on specified parameters. In this case, the researchers wanted to identify several groups among all the people who eventually developed diabetes each with a distinct pattern of BMI development. Having identified such groups, they also examined how a variety of tests associated with diabetes risk, and risks for heart disease and stroke changed in the identified groups over time.
They identified three different patterns of BMI changes in the 645 participants who developed diabetes. The vast majority (606 individuals, or 94%) belonged to a group they called “stable-overweight.” These people showed no dramatic change in their BMI in the years before they were diagnosed. They were overweight when they first entered the study and gained or lost little weight during the follow-up years. They showed only minor signs of insulin-resistance, starting five years before they developed diabetes. A second, much smaller group of 15 people gained weight consistently in the years before diagnosis. As they were gaining weight, these people also had raises in blood pressure and substantial gains in insulin resistance. The 26 remaining participants who formed the third group were persistently obese for the entire time they participated in the study, in some cases up to 18 years before they were diagnosed with diabetes. They had some signs of insulin resistance in the years before diagnosis, but not the substantial gain often seen as the hallmark of “pre-diabetes.”
What Do These Findings Mean?
These results suggest that diabetes development is a complicated process, and one that differs between individuals who end up with the disease. They call into question the common notion that most people who develop diabetes have recently gained a lot of weight or are obese. A substantial rise in insulin resistance, another established risk factor for diabetes, was only seen in the smallest of the groups, namely the people who gained weight consistently for years before they were diagnosed. When the scientists applied a commonly used predictor of diabetes called the “Framingham diabetes risk score” to their largest “stably overweight” group, they found that these people were not classified as having a particularly high risk, and that their risk scores actually declined in the last five years before their diabetes diagnosis. This suggests that predicting diabetes in this group might be difficult.
The researchers applied their methodology only to this one cohort of white civil servants in England. Before drawing more firm conclusions on the process of diabetes development, it will be important to test whether similar results are seen in other cohorts and among more diverse individuals. If the three groups identified here are found in other cohorts, another question is whether they are as unequal in size as in this example. And if they are, can the large group of stably overweight people be further subdivided in ways that suggest specific mechanisms of disease development? Even without knowing how generalizable the provocative findings of this study are, they should stimulate debate on how to identify people at risk for diabetes and how to prevent the disease or delay its onset.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001602.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes; it includes people's stories about diabetes
The charity Diabetes UK also provides detailed information about diabetes for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes
MedlinePlus provides links to further resources and advice about diabetes (in English and Spanish)
More information about the Whitehall II study is available
doi:10.1371/journal.pmed.1001602
PMCID: PMC3921118  PMID: 24523667
23.  A cross-sectional study of glucose regulation in young adults with very low birth weight: impact of male gender on hyperglycaemia 
BMJ Open  2012;2(1):e000327.
Objectives
To investigate glucose regulation in young adults with very low birth weight (VLBW; <1500 g) in an Asian population.
Design
Cross-sectional observational study.
Setting
A general hospital in Hamamatsu, Japan.
Participants
111 young adults (42 men and 69 women; aged 19–30 years) born with VLBW between 1980 and 1990. Participants underwent standard 75 g oral glucose tolerance test (OGTT).
Primary and secondary outcome measures
The primary outcomes were glucose and insulin levels during OGTT and risk factors for a category of hyperglycaemia defined as follows: diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and non-diabetes/IGT/IFG with elevated 1 h glucose levels (>8.6 mmol/l). The secondary outcomes were the pancreatic β cell function (insulinogenic index and homeostasis model of assessment for beta cell (HOMA-β)) and insulin resistance (homeostasis model of assessment for insulin resistance (HOMA-IR)).
Results
Of 111 young adults with VLBW, 21 subjects (19%) had hyperglycaemia: one had type 2 diabetes, six had IGT, one had IFG and 13 had non-diabetes/IGT/IFG with elevated 1 h glucose levels. In logistic regression analysis, male gender was an independent risk factor associated with hyperglycaemia (OR 3.34, 95% CI 1.08 to 10.3, p=0.036). Male subjects had significantly higher levels of glucose and lower levels of insulin during OGTT than female subjects (p<0.001 for glucose and p=0.005 for insulin by repeated measures analysis of variance). Pancreatic β cell function was lower in men (insulinogenic index: p=0.002; HOMA-β: p=0.001), although no gender difference was found in insulin resistance (HOMA-IR: p=0.477). In male subjects, logistic regression analysis showed that small for gestational age was an independent risk factor associated with hyperglycaemia (OR 33.3, 95% CI 1.67 to 662.6, p=0.022).
Conclusions
19% of individuals with VLBW already had hyperglycaemia in young adulthood, and male gender was a significant independent risk factor of hyperglycaemia. In male young adults with VLBW, small for gestational age was associated with hyperglycaemia.
Article summary
Article focus
Neonatal intensive care has improved the survival rate for very low birth weight infants (VLBW; birth weight <1500 g) in recent decades, and the first generation of VLBW infants have only recently reached young adulthood.
Only a few studies have shown that VLBW (or preterm) is associated with glucose intolerance in Caucasian young adults, while glucose regulation in Asian young adults with VLBW is still uncertain.
The present study investigated glucose regulation in young adults with VLBW in an Asian population and determined the factors associated with hyperglycaemia.
Key messages
Of 111 young adults with VLBW, 19% of individuals already had hyperglycaemia (type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and non-diabetes/IGT/IFG with elevated 1 h glucose levels).
Male gender was a significant independent risk factor of hyperglycaemia in young adults with VLBW.
Small for gestational age was associated with hyperglycaemia particularly in male young adults with VLBW.
Strengths and limitations of this study
This is the first study assessing the glucose regulation in young adults with VLBW in an Asian population.
This study does not provide information on postnatal growth patterns, which have been shown to be associated with later hyperglycaemia in previous studies.
The study design with no control subjects makes it impossible to address the delayed impact of VLBW itself on glucose regulation.
doi:10.1136/bmjopen-2011-000327
PMCID: PMC3274711  PMID: 22307095
24.  Aboriginal health. 
OBJECTIVE: To inform health care workers about the health status of Canada's native people. DATA SOURCES: A MEDLINE search for articles published from Jan. 1, 1989, to Nov. 31, 1995, with the use of subject headings "Eskimos" and "Indians, North American," excluding specific subject headings related to genetics and history. Case reports were excluded. Material was also identified from a review of standard references and bibliographies and from consultation with experts. STUDY SELECTION: Review and research articles containing original data concerning epidemiologic aspects of native health. Studies of Canadian populations were preferred, but population-based studies of US native peoples were included if limited Canadian information was available. DATA EXTRACTION: Information about target population, methods and conclusions was extracted from each study. RESULTS: Mortality and morbidity rates are higher in the native population than in the general Canadian population. The infant mortality rates averaged for the years 1986 to 1990 were 13.8 per 1000 live births among Indian infants, 16.3 per 1000 among Inuit infants, and only 7.3 per 1000 among all Canadian infants. Age-standardized all-cause mortality rates among residents of reserves averaged for the years 1979 to 1983 were 561.0 per 100,000 population among men and 334.6 per 100,000 among women, compared with 340.2 per 100,000 among all Canadian men and 173.4 per 100,000 among all Canadian women. Compared with the general Canadian population, specific native populations have an increased risk of death from alcoholism, homicide, suicide and pneumonia. Of the aboriginal population of Canada 15 years of age and older, 31% have been informed that they have a chronic health problem. Diabetes mellitus affects 6% of aboriginal adults, compared with 2% of all Canadian adults. Social problems identified by aboriginal people as a concern in their community include substance abuse, suicide, unemployment and family violence. Subgroups of aboriginal people are at a greater-than-normal risk of infectious diseases, injuries, respiratory diseases, nutritional problems (including obesity) and substance abuse. Initial data suggest that, compared with the general population, some subgroups of the native population have a lower incidence of heart disease and certain types of cancer. However, knowledge about contributing factors to the health status of aboriginal people is limited, since the literature generally does not assess confounding factors such as poverty. CONCLUSIONS: Canadian aboriginal people die earlier than their fellow Canadians, on average, and sustain a disproportionate share of the burden of physical disease and mental illness. However, few studies have assessed poverty as a confounding factor. Future research priorities in native health are best determined by native people themselves.
PMCID: PMC1334995  PMID: 8956834
25.  Evaluation of the combined use of adiponectin and C-reactive protein levels as biomarkers for predicting the deterioration in glycaemia after a median of 5.4 years 
Diabetologia  2011;54(10):2552-2560.
Aims/hypothesis
Hypoadiponectinaemia and raised C-reactive protein (CRP) level are obesity-related biomarkers associated with glucose dysregulation. We evaluated the combined use of these two biomarkers in predicting the deterioration of glycaemia in a prospective study after a median of 5.4 years.
Methods
In total 1,288 non-diabetic participants from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, with high-sensitivity CRP (hsCRP) and total adiponectin levels measured were included. OGTT was performed in all participants. Two hundred and six participants had deterioration of glycaemia at follow-up, whereas 1,082 participants did not.
Results
Baseline age, hsCRP and adiponectin levels were significant independent predictors of the deterioration of glycaemia in a Cox regression analysis after adjusting for baseline age, sex, BMI, hypertension, triacylglycerols, 2 h post-OGTT glucose and homeostasis model assessment of insulin resistance index (all p < 0.01). The introduction of hsCRP or adiponectin level to a regression model including the other biomarker improved the prediction of glycaemic progression significantly in all participants, especially in women (all p < 0.01). The combined inclusion of the two biomarkers resulted in a modest improvement in model discrimination, compared with the inclusion of either one alone. Among participants with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) at baseline, hsCRP and adiponectin levels were not predictive of progression or improvement of glycaemic status.
Conclusions/interpretation
Adiponectin and hsCRP levels are independent factors in predicting the deterioration of glycaemia, supporting the role of adiposity-related inflammation in the development of type 2 diabetes. Their combined use as predictive biomarkers is especially useful in women, but not in participants with IFG/IGT.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-011-2227-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-011-2227-0
PMCID: PMC3168746  PMID: 21727999
Adiponectin; Biomarker; C-reactive protein; Glycaemia

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