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1.  Retinol-Binding Protein 4 Is Associated With Prediabetes in Adults From the General Population 
Diabetes Care  2011;34(7):1648-1650.
OBJECTIVE
We examined the association between retinol-binding protein 4 (RBP4), a novel adipokine, and prediabetes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in men and women aged 32–81 years.
RESEARCH DESIGN AND METHODS
The analysis was based on 2,614 participants without previously diagnosed diabetes and those with newly diagnosed diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study, conducted from 2006 to 2008 in southern Germany. Plasma RBP4 was analyzed by immunonephelometry.
RESULTS
In logistic regression analysis, RBP4 levels in the fourth quartile versus the first quartile were significantly associated with prediabetes (i-IGT, i-IFG, and IFG/IGT; reference normal glucose tolerance) independent of known metabolic risk factors and lifestyle variables (odds ratio 1.63 [95% CI 1.17–2.27] after multivariable adjustment). Stratification by sex showed generally similar results.
CONCLUSIONS
RBP4 levels were associated with prediabetes in individuals from the general population. Prospective studies investigating the impact of RBP4 on the development of glucose intolerance are needed.
doi:10.2337/dc11-0118
PMCID: PMC3120167  PMID: 21617096
2.  Impaired Fasting Glucose in Cystic Fibrosis 
Diabetes Care  2010;33(12):2660-2664.
OBJECTIVE
While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.
RESEARCH DESIGN AND METHODS
Data were retrieved from the University of Minnesota CF database on oral glucose tolerance tests (OGTTs) performed in 1996–2005. Subjects were identified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CF–related diabetes without fasting hyperglycemia (CFRD FH−). Patients with fasting hyperglycemia were excluded. The presence of IFG was assessed within each category. In a separate case-control cohort study, subjects with IFG were matched to CF control subjects by age, sex, and OGTT class to explore outcomes.
RESULTS
For the total population (n = 310), the prevalence of IFG was 22%, and by OGTT class was NGT 14%, IGT 31%, CFRD FH− 53%. Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04–0.9]). IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29–1.48]). Lung function was better in pediatric IFG subjects with IGT and not significantly worse in adults with IGT or adults and children with NGT and CFRD FH−. BMI was not significantly different in IFG subjects versus control subjects.
CONCLUSIONS
Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.
doi:10.2337/dc10-0613
PMCID: PMC2992208  PMID: 21115768
3.  Diabetes and Other Disorders of Glycemia in a Rural South African Community 
Diabetes Care  2008;31(9):1783-1788.
OBJECTIVE—The purpose of this study was to determine the prevalence of diabetes, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG), and associated risk factors in a rural South African black community.
RESEARCH DESIGN AND METHODS—This was a cross-sectional survey conducted by random cluster sampling of adults aged >15 years. Participants had a 75-g oral glucose tolerance test using the 1998 World Health Organization criteria for disorders of glycemia.
RESULTS—Of 1,300 subjects selected, 1,025 subjects (815 women) participated (response rate 78.9%). The overall age-adjusted prevalence of diabetes was 3.9%, IGT 4.8%, and IFG 1.5%. The prevalence was similar in men and women for diabetes (men 3.5%; women 3.9%) and IGT (men 4.6%; women 4.7%) but higher in men for IFG (men 4.0%; women 0.8%). The prevalence of diabetes and IGT increased with age both in men and women, with peak prevalence in the 55- to 64-year age-group for diabetes and in the ≥65-year age-group for IGT. Of the cases of diabetes, 84.8% were discovered during the survey. In multivariate analysis, the significant independent risk factors associated with diabetes included family history (odds ratio 3.5), alcohol ingestion (2.8), waist circumference (1.1), systolic blood pressure (1.0), serum triglycerides (2.3), and total cholesterol (1.8); hip circumference was protective (0.9).
CONCLUSIONS—There is a moderate prevalence of diabetes and a high prevalence of total disorders of glycemia, which suggests that this community, unlike other rural communities in Africa, is well into an epidemic of glucose intolerance. There is a low proportion of known diabetes and a significant association with potentially modifiable risk factors.
doi:10.2337/dc08-0212
PMCID: PMC2518345  PMID: 18523142
4.  Prevalence and correlates of hyperglycemia in a rural population, Vietnam: implications from a cross–sectional study 
BMC Public Health  2012;12:939.
Background
Despite the increasing prevalence of type 2 diabetes in urban areas, relatively little has been known about its actual prevalence and its associations in rural areas, Vietnam. The purpose of this study was to evaluate the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), diabetes and their risk factors in a rural province, Vietnam.
Methods
A cross–sectional study with a representative sample was designed to estimate the hyperglycemia prevalence, using 75–g oral glucose tolerance test. Potential risk factors for hyperglycemia were analyzed using multinomial logistic regression, taken into account influences of socio–economic status, anthropometric measures, and lifestyle–related factors.
Results
The age and sex–adjusted prevalence rates (95% CI) of isolated IFG, isolated IGT, combined IFG–IGT, and diabetes were 8.7 (7.0–10.5), 4.3 (3.2−5.4), 1.6 (0.9−2.3), and 3.7% (2.7–4.7%), respectively. There were still 73% of diabetic subjects without knowing the condition. Blood pressure, family history of diabetes, obesity–related measures (waist circumference, waist–hip ratio, body fat percentage, and abdominal obesity) were the independent risk factors for hyperglycemia (IFG, IGT, and diabetes).
Conclusions
The prevalence of hyperglycemia in rural areas has not been as sharply increased as that reported in urban cities, Vietnam. Blood pressure and obesity–related measures were the most significant predictors for hyperglycemia level and they can be taken into account in building prognosis models to early detection of diabetes in rural Vietnamese populations.
doi:10.1186/1471-2458-12-939
PMCID: PMC3548760  PMID: 23114020
Type 2 diabetes; Population–based study; Prevalence; Risk factors; Vietnamese
5.  Prevalence of Type 2 Diabetes and Impaired Glucose Regulation with Associated Cardiometabolic Risk Factors and Depression in an Urbanizing Rural Community in Bangladesh: A Population-Based Cross-Sectional Study 
Diabetes & Metabolism Journal  2012;36(6):422-432.
Background
To determine the prevalence of type 2 diabetes (T2DM) and impaired glucose regulation (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT]) in an urbanizing rural population of Bangladesh and associated cardiometabolic risk indicators and depression.
Methods
A total of 2,293 subjects aged ≥20 years in an urbanizing rural Bangladeshi community were investigated. Socio-demographic and anthropometric details, blood pressure, fasting plasma glucose (FPG), 2 hours after 75 g plasma glucose (2hPG), glycosylated hemoglobin, fasting serum insulin and lipid profiles were studied. Presence of depressive symptoms using Montogomery-Asberg Depression Rating Scale was also assessed.
Results
The prevalence of IFG, IGT, IFG+IGT, and T2DM were 3.4%, 4.0%, 1.2%, and 7.9%, respectively. The prevalence of T2DM and impaired glucose regulation differed between males and females, but, both increased with age in both sexes. FPG and 2hPG had positive correlation. Employing logistic regression, it was found that increased age, waist to hip ratio, systolic blood pressure, total cholesterol, triglycerides, and depression were independent risk indicators for diabetes. Both insulin resistance and β-cell deficiency were significantly related for causation of diabetes. Among the study population, 26.2% had general obesity, 39.8% central obesity, 15.5% hypertension, 28.7% dyslipidemia, 17.6% family history of diabetes, and 15.3% had depression. Physical inactivity and smoking habits were significantly higher in male.
Conclusion
Rising prevalence of diabetes and impaired glucose regulation in this urbanizing rural population exist as a significant but hidden public health problem. Depression and other cardiometabolic risk indicators including obesity, hypertension, and dyslipdemia were also prevalent in this population.
doi:10.4093/dmj.2012.36.6.422
PMCID: PMC3530713  PMID: 23275936
Bangladesh; Diabetes mellitus; Impaired glucose regulation; Prevalence
6.  Postchallenge Hyperglycemia Is Positively Associated With Diabetic Polyneuropathy 
Diabetes Care  2012;35(9):1891-1893.
OBJECTIVE
To assess the prevalence of distal sensorimotor polyneuropathy (DSPN) in an older population and to examine its relationship with prediabetes.
RESEARCH DESIGN AND METHODS
Glucose tolerance status was determined in 61- to 82-year-old participants (n = 1,100) of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 Survey (2006–2008). Clinical DSPN was defined as bilaterally impaired foot-vibration perception and/or foot-pressure sensation.
RESULTS
Prevalence of clinical DSPN was similar in subjects with known diabetes (22.0%) and subjects with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (23.9%). Among prediabetic subgroups, IFG-IGT, but not isolated-IFG and -IGT, was associated with a higher risk of clinical DSPN, compared with normal glucose tolerance. A J-shaped association was observed between clinical DSPN and quartiles of 2-h postchallenge glucose, but not with fasting glucose and HbA1c levels.
CONCLUSIONS
Subjects with IFG-IGT and known diabetes had a similar prevalence of clinical DSPN. Elevated 2-h postload glucose levels appeared important for disease risk.
doi:10.2337/dc11-2028
PMCID: PMC3424984  PMID: 22751964
7.  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
8.  Fasting tests of insulin secretion and sensitivity predict future prediabetes in Japanese with normal glucose tolerance 
Abstract
Aims/Introduction:  Reduced insulin sensitivity and secretion are important in the pathogenesis of type 2 diabetes. Their relationships to prediabetes, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) have been previously studied with the oral glucose tolerance test (OGTT). We investigated whether or not baseline measures of insulin secretion and sensitivity obtained from fasting blood specimens were related to the development of prediabetes and how these measures compared with those based on the OGTT.
Materials and Methods:  In 152 Japanese subjects with normal glucose tolerance, we measured baseline plasma glucose and insulin after an overnight fast and during a 75 g OGTT, insulin resistance index (homeostasis model assessment [HOMA‐IR]), and insulin secretion (insulinogenic index [30 min insulin − fasting insulin] ÷ [30 min glucose − fasting glucose] or HOMA‐β).
Results:  At a 5–6 year (mean 5.7 years) follow‐up examination, we confirmed 36 cases of prediabetes. After adjusting for age, sex, family history of diabetes, body mass index, and 2‐h plasma glucose, the odds ratio comparing the lowest tertile (≤0.82) of insulinogenic index with the highest tertile (≥1.43) was 6.98 (95% confidence interval, 1.96–24.85) and was 10.72 (2.08–55.3) comparing the lowest tertile (≤76.3) of HOMA‐β with the highest tertile (≥122.1), whereas the respective odds ratios of HOMA‐IR were 3.74 (1.03–13.57) and 10.89 (1.93–61.41) comparing the highest tertile (≥1.95) with the lowest tertile (≤1.25).
Conclusions:  Lower insulin secretion and sensitivity are independent risk factors for prediabetes. Clinically practical identification of those at risk for prediabetes is obtainable from HOMA‐β and HOMA‐IR, both of which are measured in fasting state. (J Diabetes Invest, doi: 10.1111.j.2040‐1124.2010.00041.x, 2010)
doi:10.1111/j.2040-1124.2010.00041.x
PMCID: PMC4020720  PMID: 24843431
Glucose intolerance; Insulin resistance; Epidemiology
9.  Potential association between prediabetic conditions and gingival and/or periodontal inflammation 
Aims/Introduction
Prediabetic conditions, which include impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), might be associated with chronic gingival and/or periodontal inflammation. However, the occurrence of this oral inflammation in prediabetic conditions is poorly understood. The present study aimed to assess the association between prediabetes and gingival and/or periodontal inflammation.
Materials and Methods
A total of 94 Puerto Rican men and women aged 40–65 years, who were residents of San Juan, Puerto Rico, and free of diabetes, were included in the study. All participants had at least one tooth site with clinical attachment loss ≥3 mm. Fasting and 2-h plasma glucose were collected. Gingival/periodontal inflammation was assessed by bleeding on gentle probing of the sulcus at six sites per tooth.
Results
Participants with the percentage of teeth with bleeding on probing (BOP) equal to or greater than the median were compared with those with the percentage of teeth with BOP less than median. Participants with high BOP tended to present higher IFG (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.2–25.3) and/or prediabetic condition (OR 3.6, 95% CI 1.0–13.2) than those with a low percentage of BOP, adjusting for age, sex, smoking, alcohol consumption, waist circumference and number of missing teeth. Using the continuous form of the outcome, the corresponding adjusted least squares means of percentage of BOP were 26.8 (standard error of the mean [SEM] 2.3) and 43.8 (SEM 6.0) in normal and IFG, respectively (P = 0.01), and 27.0 (SEM 2.4) and 39.0 (SEM 5.3) among healthy and prediabetic individuals, respectively (P = 0.05).
Conclusion
IFG and/or prediabetes are strongly associated with BOP, a marker of chronic gingival/periodontal inflammation.
doi:10.1111/jdi.12122
PMCID: PMC3980950  PMID: 24729853
Gingival/periodontal inflammation; Impaired glucose; Prediabetes
10.  Potential association between prediabetic conditions and gingival and/or periodontal inflammation 
Abstract
Aims/Introduction
Prediabetic conditions, which include impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), might be associated with chronic gingival and/or periodontal inflammation. However, the occurrence of this oral inflammation in prediabetic conditions is poorly understood. The present study aimed to assess the association between prediabetes and gingival and/or periodontal inflammation.
Materials and Methods
A total of 94 Puerto Rican men and women aged 40–65 years, who were residents of San Juan, Puerto Rico, and free of diabetes, were included in the study. All participants had at least one tooth site with clinical attachment loss ≥3 mm. Fasting and 2‐h plasma glucose were collected. Gingival/periodontal inflammation was assessed by bleeding on gentle probing of the sulcus at six sites per tooth.
Results
Participants with the percentage of teeth with bleeding on probing (BOP) equal to or greater than the median were compared with those with the percentage of teeth with BOP less than median. Participants with high BOP tended to present higher IFG (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.2–25.3) and/or prediabetic condition (OR 3.6, 95% CI 1.0–13.2) than those with a low percentage of BOP, adjusting for age, sex, smoking, alcohol consumption, waist circumference and number of missing teeth. Using the continuous form of the outcome, the corresponding adjusted least squares means of percentage of BOP were 26.8 (standard error of the mean [SEM] 2.3) and 43.8 (SEM 6.0) in normal and IFG, respectively (P = 0.01), and 27.0 (SEM 2.4) and 39.0 (SEM 5.3) among healthy and prediabetic individuals, respectively (P = 0.05).
Conclusion
IFG and/or prediabetes are strongly associated with BOP, a marker of chronic gingival/periodontal inflammation.
doi:10.1111/jdi.12122
PMCID: PMC3980950  PMID: 24729853
Gingival/periodontal inflammation; Impaired glucose; Prediabetes
11.  Uric Acid Is More Strongly Associated with Impaired Glucose Regulation in Women than in Men from the General Population: The KORA F4-Study 
PLoS ONE  2012;7(5):e37180.
Objective
High serum uric acid (UA) levels are associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. It is largely unknown whether there are gender-specific differences regarding the association between UA and prediabetic states. We examined the possible association between UA levels and known as well as newly diagnosed diabetes (NDD), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT in a population-based sample of 32-to-81-year-old men and women.
Research Design and Methods
An oral glucose tolerance test was carried out in all 2,740 participants without known diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study conducted between 2006 and 2008 in Southern Germany. Serum UA was analysed by the uricase method.
Results
In women after multivariable adjustment the associations between UA and i-IFG (OR 1.57, 95% CI 1.15–2.14), IFG/IGT (OR 1.52, 1.07–2.16), NDD (OR 1.67, 95% CI 1.28–2.17), and known diabetes (OR 1.47, 95% CI 1.18–1.82) remained significant, but the association with i-IGT (OR 1.14, 95% CI 0.95–1.36) lost significance. In contrast in men, after multivariable adjustment there was only a significant association between UA levels and i-IFG (OR 1.49, 95% CI 1.21–1.84), all other associations were non-significant (i-IGT: OR 1.09, IFG/IGT: OR 1.06, NDD: OR 0.91, known diabetes: OR 1.04; all p-values>0.05).
Conclusions
Serum UA concentrations were associated with different categories of impaired glucose regulation in individuals from the general population, particularly in women. Further studies investigating the role of UA in the development of derangements in glucose metabolism are needed.
doi:10.1371/journal.pone.0037180
PMCID: PMC3353894  PMID: 22615932
12.  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
13.  Should the first degree relatives of type 2 diabetic patients with isolated impaired fasting glucose be considered for a diabetes primary prevention program? 
BACKGROUND:
The aim of this study is to investigate the need for diabetes primary prevention program in isolated impaired fasting glucose (i-IFG) of the first degree relatives of type 2 diabetics.
METHODS:
In a cross sectional study, 793 individuals with prediabetes [543 with i-IFG and 250 with isolated impaired glucose tolerance (i-IGT)] who were the first degree relatives of type 2 diabetic patients, were enrolled. Isolated IFG was considered as fasting plasma glucose between 100-125 mg/dl and 2 hour plasma glucose < 140 mg/dl and isolated IGT as FPG < 100 mg/dl and 2 hour plasma glucose between 140-199 mg/dl during an overnight fasting 75 g oral glucose tolerance test. Mean of the age, weight, waist circumference, body mass index, systolic and diastolic blood pressure, plasma glucose, HbA1C, and lipid profile were compared between two groups (i-IFG and i-IGT). The prevalence of cardiometabolic risk factors (BMI ≥ 25 kg/m2, hypertension, cholesterol ≥ 200 mg/dl, LDL-C ≥ 100 mg/dl, HDL-C ≤ 40 mg/dl, and triglyceride ≥ 150 mg/dl) adjusted by age, sex and BMI were compared.
RESULTS:
The prevalence of cardiometabolic risk factors is higher in i-IFG group than i-IGT. The mean level of LDL-C is significantly higher in i-IFG than i-IGT group.
CONCLUSIONS:
First degree relatives of T2DM with isolated impaired fasting glucose should probably be included in the primary preventive program for diabetes. However, longitudinal cohort study is required to show high progression of i-IFG to T2DM.
PMCID: PMC3082819  PMID: 21526094
Prediabetic States; Diabetes Mellitus; Type II; Oral Glucose Tolerance Test; Primary Prevention; Dyslipidemia; Risk Factor; Iran
14.  Prevalence and Timing of Postpartum Glucose Testing and Sustained Glucose Dysregulation After Gestational Diabetes Mellitus 
Diabetes Care  2009;33(3):569-576.
OBJECTIVE
To estimate the prevalence of postpartum glucose testing within 6 months of pregnancies complicated by gestational diabetes mellitus (GDM), assess factors associated with testing and timing of testing after delivery, and report the test results among tested women.
RESEARCH DESIGN AND METHODS
This was a retrospective study of 11,825 women who were identified as having GDM using the 100-g oral glucose tolerance test (OGTT) from 1999 to 2006. Postpartum testing (75-g 2-h OGTT or fasting plasma glucose [FPG]) within 6 months of delivery and test results from laboratory databases are reported. Postpartum test results are categorized as normal, impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), and provisionally diabetic.
RESULTS
About half (n = 5,939) the women were tested with either a FPG or 75-g OGTT from 7 days to 6 months postpartum. Of these women, 46% were tested during the 6- to 12-week postpartum period. Odds of testing were independently associated with age, race/ethnicity, household income, education, foreign-born status, parity, mode of delivery, having a postpartum visit, having GDM coded at discharge, and pharmacotherapy for GDM. Of the 5,857 women with test results, 16.3% (n = 956) had IFG/IGT and 1.1% (n = 66) had provisional diabetes. After adjustment for demographic and clinical factors, abnormal postpartum test results was associated with having required insulin, glyburide, or metformin during pregnancy and with longer period from delivery to postpartum testing.
CONCLUSIONS
After a pregnancy complicated by GDM, automated orders for postpartum testing with notification to physicians and electronically generated telephone and e-mail reminder messages to patients may improve the rates of postpartum testing for persistence of glucose intolerance.
doi:10.2337/dc09-2095
PMCID: PMC2827509  PMID: 20040657
15.  Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance 
Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated.
Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed.
Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05).
Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.
doi:10.7150/ijms.4128
PMCID: PMC3444978  PMID: 22991496
β cell function; insulin resistance; insulin sensitivity; newly-diagnosed diabetes mellitus; pre-diabetes; total glucagon-like peptide-1.
16.  Correlation Between Prediabetes Conditions and Microalbuminuria 
Nephro-urology Monthly  2013;5(2):741-744.
Background
Impaired fasting glucose (IFG), and impaired glucose tolerance (IGT) are two prediabetes conditions which have some correlation with macrovascular disorders. The risk of microvascular complications in these groups is not clear.
Objectives
The prevalence of albuminuria in subjects with IFG and IGT was evaluated in the present study.
Patients and Methods
In this study three groups of subjects were entered (45 subjects in each group): IFG, IGT, and normal glucose tolerance as control. The urine albumin-creatinine ratio was studied in morning spot urine samples to detect microalbuminuria. The subjects were followed up for two years, and blood sugar and urine albumin and glycosylated hemoglobin (HbA1C) were measured every 6 months.
Results
The prevalence rate of microalbuminuria was 15.5% in the prediabetic groups, while no one had microalbuminuria in the control group (P = 0.005). The prevalence of microalbuminuria in patients with IFG or IGT was not significantly different (17.8% vs. 13.3%) (P = 0.4). Fourteen subjects (4 in IFG group and 10 in IGT group) developed diabetes mellitus within a 2-year follow-up period (P = 0.1). Thirty six percent of subjects with albuminuria, and twelve percent of subjects without albuminuria progressed to diabetes mellitus during a 2-year follow-up (P = 0.02, odd ratio = 4.1; CI95%, 1.13-15.1).
Conclusions
The risk of microalbuminuria in prediabetic subjects is high, and probably prediabetic subjects are at higher risk of progression to diabetes mellitus. We suggest periodically evaluation of albuminuria in prediabetic patients after the diagnosis.
doi:10.5812/numonthly.7646
PMCID: PMC3703132  PMID: 23841037
Glucose Tolerance; Diabetic Nephropathies; Diabetes Mellitus, Type 2
17.  Routine OGTT: A Robust Model Including Incretin Effect for Precise Identification of Insulin Sensitivity and Secretion in a Single Individual 
PLoS ONE  2013;8(8):e70875.
In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10−5±9.36×10−5 min−1pM−1), IFG (5.30×10−5±5.18×10−5) and combined IGT, IFG+IGT and T2DM (2.09×10−5±1.95×10−5, 2.38×10−5±2.28×10−5 and 2.38×10−5±2.09×10−5 respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups. The SIMO model may therefore be of value for the quantification of glucose homeostasis from clinical OGTT data.
doi:10.1371/journal.pone.0070875
PMCID: PMC3756988  PMID: 24009656
18.  Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults 
Increasing evidence suggests that the insulin-like growth factor (IGF)-system may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women ≥65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95% CI: 0.26, 0.64; p-trend: <0.01) for IFG. We did not find any significant association between IGF-I and glucose intolerance in this study and the association for IGFBP-3 was less clear. However, low levels of IGF-I and IGFBP-3 were associated with increased levels of markers of inflammation including C-reactive protein and interleukin-6 levels. We conclude that a among adults ≥ 65 years, low IGFBP-1 levels are associated with increased prevalence of glucose intolerance. We did not confirm prior associations of low IGF-I with glucose intolerance in this cohort of older individuals.
doi:10.1016/j.ghir.2007.08.004
PMCID: PMC2492581  PMID: 17904401
19.  Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease 
Liver International  2009;29(4):525-529.
Objective
The association of nonalcoholic fatty liver disease (NAFLD) with insulin resistance and metabolic syndrome has been documented for obese men and middle-aged men. This study was designed to determine the relationship between NAFLD and the oral glucose tolerance test (OGTT) to predict preclinical diabetes in nondiabetic young male patients (<30 years old).
Methods
A total of 75 male patients who had elevated liver enzymes and who were diagnosed with NAFLD were enrolled in this study. A standard 75 g OGTT was carried out on all patients. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined as a fasting plasma glucose (FPG) level ≥100 mg/dl but <126 mg/dl, and a 2-h post-load glucose on the OGTT of ≥140 mg/dl, but <200 mg/dl respectively.
Results
According to the OGTT results, 24 (32%) patients were diagnosed as having IGT and 12 (16%) patients were diagnosed as having diabetes. Among the 48 patients with normal fasting glucose, 18 (37.6%) patients showed abnormal glucose tolerance (15 had IGT and three had diabetes). The NAFLD patients with abnormal glucose tolerance showed significant differences in age, weight, body mass index, waist–hip ratio, alanine aminotransferase, total bilirubin, total cholesterol, low-density lipoprotein cholesterol, triglyceride, insulin, FPG and homeostasis model for insulin resistance (HOMA-IR). Multiple regression analysis showed that age, FPG and HOMA-IR were independent predictors of abnormal glucose tolerance.
Conclusions
Although the patients were young men, an OGTT should be recommended for NAFLD patients with elevated liver enzymes and IFG to predict the risk of type 2 diabetes.
doi:10.1111/j.1478-3231.2008.01920.x
PMCID: PMC2711255  PMID: 19323780
insulin resistance; nonalcoholic fatty liver disease; oral glucose tolerance test
20.  Prevalence of Pre-Diabetes and Its Association With Clustering of Cardiometabolic Risk Factors and Hyperinsulinemia Among U.S. Adolescents 
Diabetes Care  2009;32(2):342-347.
OBJECTIVE—Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are considered to constitute “pre-diabetes.” We estimated the prevalence of IFG, IGT, and pre-diabetes among U.S. adolescents using data from a nationally representative sample.
RESEARCH DESIGN AND METHODS—We analyzed data from participants aged 12–19 years in the National Health and Nutrition Examination Survey 2005–2006. We used fasting plasma glucose and 2-h glucose during an oral glucose tolerance test to assess the prevalence of IFG, IGT, and pre-diabetes and used the log-binomial model to estimate the prevalence ratios (PRs) and 95% CIs.
RESULTS—The unadjusted prevalences of IFG, IGT, and pre-diabetes were 13.1, 3.4, and 16.1%, respectively. Boys had a 2.4-fold higher prevalence of pre-diabetes than girls (95% CI 1.3–4.3). Non-Hispanic blacks had a lower rate than non-Hispanic whites (PR 0.6, 95% CI 0.4–0.9). Adolescents aged 16–19 years had a lower rate than those aged 12–15 years (0.6, 0.4–0.9). Overweight adolescents had a 2.6-fold higher rate than those with normal weight (1.3–5.1). Adolescents with two or more cardiometabolic risk factors had a 2.7-fold higher rate than those with none (1.5–4.8). Adolescents with hyperinsulinemia had a fourfold higher prevalence (2.2–7.4) than those without. Neither overweight nor number of cardiometabolic risk factors was significantly associated with pre-diabetes after adjustment for hyperinsulinemia.
CONCLUSIONS—Pre-diabetes was highly prevalent among adolescents. Hyperinsulinemia was independently associated with pre-diabetes and may account for the association of overweight and clustering of cardiometabolic risk factors with pre-diabetes.
doi:10.2337/dc08-1128
PMCID: PMC2628705  PMID: 18957533
21.  Disorders of Glucose Metabolism in HIV-Infected Women 
Background
Abnormal glucose metabolism in HIV-infected patients has largely been attributed to protease inhibitor use. However most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate controls.
Methods
We assessed factors associated with previously-diagnosed diabetes among 620 midlife women with- or at-risk for HIV infection. In a subset of 221 women without previously-diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) with insulin levels, and assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion.
Results
Thirteen percent had previously-diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had undiagnosed diabetes and 12% had impaired glucose tolerance (IGT). On multivariate analysis, factors associated with previously-diagnosed diabetes included current methadone treatment, body mass index, family history of diabetes, and physical inactivity. Factors independently associated with abnormal OGTT (IGT or diabetes) included age ≥50 y, family history of diabetes, physical inactivity, and pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and among HIV-infected women, use of non-PI HAART. Factors associated with lower insulin secretion included current opiate use (methadone or heroin) and older age.
Conclusions
Abnormal glucose metabolism is highly prevalent among midlife women with or at-risk for HIV infection, particularly those who use opiates. Women with classic diabetes risk factors, rather than solely those taking PIs, should be screened for diabetes in the primary care setting. Interventions targeting modifiable risk factors, including obesity and physical inactivity, are also warranted.
doi:10.1086/429824
PMCID: PMC2104646  PMID: 15844072
human immunodeficiency virus (HIV); diabetes mellitus; antiretroviral therapy; women; drug use
22.  Can Admission and Fasting Glucose Reliably Identify Undiagnosed Diabetes in Patients With Acute Coronary Syndrome?  
Diabetes Care  2008;31(10):1955-1959.
OBJECTIVE—Our objectives were to determine the prevalence of previously undiagnosed abnormal glucose tolerance, i.e., diabetes and impaired glucose tolerance (IGT) in patients with acute coronary syndrome and to assess the utility of admission and fasting glucose in identifying diabetes in these patients.
RESEARCH DESIGN AND METHODS—Glycemic status was characterized on the basis of admission plasma glucose (APG), fasting plasma glucose (FPG), and an oral glucose tolerance test (OGTT) in 140 patients admitted to the hospital with acute coronary syndrome, who were not known to have diabetes (mean ± SD age 67.3 ± 13.4 years; 79% men). OGTTs were performed on days 5–7 after admission.
RESULTS—The prevalences of diabetes and IGT were 27 and 39%, respectively, according to OGTT criteria. Receiver operating characteristic curves showed that the area under the curve for diagnosing diabetes was 0.83 (P < 0.001) for FPG, 0.79 (P < 0.001) for APG, and 0.84 (P < 0.001) for FPG and APG applied in combination. A FPG cutoff ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) yielded a sensitivity of 89.5% and a positive predictive value of 43.6% for detecting diabetes.
CONCLUSIONS—A high prevalence of abnormal glucose tolerance was seen in patients with acute coronary syndrome. The combination of FPG ≥5.6 mmol/l (100 mg/dl) and/or APG ≥7.8 mmol/l (140 mg/dl) was highly sensitive for identifying diabetes. Although weakly specific, this simple algorithm could offer a practical initial screening tool at the acute setting in the high-risk population with acute coronary syndrome.
doi:10.2337/dc08-0197
PMCID: PMC2551634  PMID: 18591399
23.  Fasting hyperglycemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults 
Diabetes, obesity & metabolism  2012;14(9):835-841.
Aim
Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes.
Methods
Seventy-six older (65.1 ± 0.6yr) obese adults with impaired fasting glucose (IFG; n=12), impaired glucose tolerance (IGT; n=9), and combined glucose intolerance (IFG+IGT = CGI; n=22) were compared to normal glucose tolerant (NGT; n=15) and T2D (n=18) groups after 12 weeks of exercise training (60 min/d for 5d/wk at ~85% HRmax). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (euglycemic hyperinsulinemic clamp at 40 mU/m2·min−1), β-cell function (glucose stimulated insulin secretion corrected for insulin sensitivity), body composition (hydrostatic weighing/CT scan), and cardiovascular fitness (treadmill VO2max) were also assessed.
Results
Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2-hour glucose levels in IGT, CGI and T2D (p < 0.05). However, 2-hour glucose levels were not normalized in adults with CGI compared to IGT (p < 0.05). β-cell function improved similarly across groups (p < 0.05). Although not statistically significant, insulin sensitivity increased approximately 40% in IFG and IGT, but only 17% in CGI.
Conclusion
The magnitude of improvement in glucose metabolism after 12-weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes.
doi:10.1111/j.1463-1326.2012.01608.x
PMCID: PMC3407343  PMID: 22510250
obesity; prediabetes; insulin resistance; beta-cell dysfunction; exercise
24.  Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance1 
Diabetic Medicine  2008;25(10):1211-1217.
Aims
We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress.
Methods
The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan–Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social–psychological factors.
Results
Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow-up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1–6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white-collar worker (HR = 0.34, P = 0.033), non-smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042).
Conclusions
In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white-collar worker, a non-smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT.
doi:10.1111/j.1464-5491.2008.02566.x
PMCID: PMC2701561  PMID: 19046200
impaired fasting glucose; impaired glucose tolerance; psychosocial factors; Type 2 diabetes
25.  Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals 
PLoS ONE  2012;7(6):e38224.
Introduction
Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists.
Methods
In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes.
Results
The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m2 but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found.
Discussion
We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk.
doi:10.1371/journal.pone.0038224
PMCID: PMC3387191  PMID: 22768041

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