Impaired glucose tolerance (IGT) and type 2 diabetes including undiagnosed isolated postchallenge hyperglycemia (IPH) are common in the elderly. The aim of this study was to investigate the insulin secretion and sensitivity in Korean elderly lean diabetic women. Forty-one lean women aged 65-88 years took 2 hr oral glucose tolerance test (OGTT) and were stratified according to the WHO criteria (normal glucose tolerance [NGT], n=20; IGT, n=6; and type 2 diabetics, n=15 including seven IPH). HbA1c and fructosamine progressively increased from the NGT to the diabetic subjects (p=0.006 and p=0.001, respectively). Compared with subjects with NGT, the insulinogenic index, a marker of early insulin secretion and the AUC(ins), a marker of total insulin secretion, decreased significantly in diabetic group [0.53 (-0.44 -1.45) vs. 0.18 (0.00 -1.11), p=0.03 and 306+/-165 vs. 199+/-78 pmol/L, p=0.02 respectively]. A significant difference was found in the AUC(c-peptide) among each group (221+/-59 vs. 206+/-34 vs. 149+/-51 pmol/L, p=0.001 for each). The homeostasis model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, was not different among the groups. We conclude that compared with NGT subjects, elderly lean women with diabetes have impaired oral glucose-induced insulin secretion but have relatively preserved insulin sensitivity. This suggests that insulin resistance is not necessarily an essential component of Korean elderly lean diabetic women.
Evidence suggests that the PPARγ-agonist insulin sensitizer pioglitazone, may provide potential beneficial cardiovascular (CV) effects beyond its anti-hyperglycaemic function. A reduced endothelial progenitor cell (EPC) number is associated with impaired glucose tolerance (IGT) or diabetes, conditions characterised by increased CV risk.
To evaluate whether pioglitazone can provide benefit in vitro in EPCs obtained from IGT subjects.
Materials and Methods
Early and late-outgrowth EPCs were obtained from peripheral blood mononuclear cells of 14 IGT subjects. The in vitro effect of pioglitazone (10 µM) with/without PPARγ-antagonist GW9662 (1 µM) was assessed on EPC viability, apoptosis, ability to form tubular-like structures and pro-inflammatory molecule expression.
Pioglitazone increased early and late-outgrowth EPC viability, with negligible effects on apoptosis. The capacity of EPCs to form tubular-like structures was improved by pioglitazone in early (mean increase 28%; p = 0.005) and late-outgrowth (mean increase 30%; p = 0.037) EPCs. Pioglitazone reduced ICAM-1 and VCAM-1 adhesion molecule expression in both early (p = 0.001 and p = 0.012 respectively) and late-outgrowth (p = 0.047 and p = 0.048, respectively) EPCs. Similarly, pioglitazone reduced TNFα gene and protein expression in both early (p = 0.034;p = 0.022) and late-outgrowth (p = 0.026;p = 0.017) EPCs compared to control. These effects were prevented by incubation with the PPARγ-antagonist GW9662.
Pioglitazone exerts beneficial effects in vitro on EPCs isolated from IGT subjects, supporting the potential implication of pioglitazone as a CV protective agents.
AIM: To investigate which obese children have an increased risk for impaired glucose tolerance (IGT), a risk factor for later diabetes.
METHODS: We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline. Waist circumference, fasting glucose, lipids, blood pressure, pubertal stage, 2 h glucose in oral glucose tolerance test (oGTT), and HbA1c were determined at baseline and 1 year later.
RESULTS: One year after baseline, 19 (11.2%) children demonstrated IGT, 4 (2.4%) children had impaired fasting glucose, no (0%) child suffered from diabetes, and 146 (86%) children still showed normal glucose tolerance. At baseline, the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter, apart from pubertal stage. The children developing IGT entered puberty significantly more frequently (37% vs 3%, P < 0.001). One year after baseline, the children with IGT demonstrated significantly increased waist circumference, blood pressure values, insulin and triglyceride concentrations, and insulin resistance index HOMA. The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes.
CONCLUSION: During the study period of 1 year, more than 10% of the obese children with normal glucose tolerance converted to IGT. Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance, waist circumference, blood pressure, or triglyceride concentrations.
Impaired glucose tolerance; Risk factors; Lipids; Blood pressure; Pubertal stage; Waist circumference
Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects.
The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function.
NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients.
These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients.
cystatin C; N-acetyl-β-d-glucosaminidase; tubular dysfunction; impaired glucose tolerance; diabetic nephropathy
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.
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.
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.
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.
Prediabetic States; Diabetes Mellitus; Type II; Oral Glucose Tolerance Test; Primary Prevention; Dyslipidemia; Risk Factor; Iran
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.
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.
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.
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.
Bangladesh; Diabetes mellitus; Impaired glucose regulation; Prevalence
Within the frame of a randomized clinical trial to examine whether training of general practitioners (the intervention group) in intensive lifestyle modification and pharmacological treatment of patients with type 2 diabetes has a spillover effect on individuals with impaired fasting glycaemia (IFG) or impaired glucose tolerance (IGT).
A high-risk screening study for type 2 diabetes with an intervention programme, where general practices were randomized to provide standard treatment versus intensive lifestyle modification and pharmacological treatment to newly diagnosed diabetic patients.
General practices in Denmark.
Of 1821 individuals identified with IFG or IGT, results from oral glucose tolerance tests after one and three years were available in 1510 individuals.
Main outcome measures
Progression rates from IFG and IGT to diabetes and effect of intervention were estimated in a regression model using interval censoring.
A total of 442 persons developed diabetes. There was no significant overall effect of intervention on progression rates. For risk factors, no difference in rate of change was found between randomization groups, but a difference was found between general practices within the same randomization groups.
General practitioners identify a high number of incident diabetes cases in individuals with IFG or IGT found by high-risk screening. Intervention at the general practitioner's level in intensive treatment type 2 diabetes does not have a significant spillover effect reducing the risk of diabetes from pre-diabetic conditions. This could indicate that intervention strategies should be specifically targeted at individuals with IFG or IGT, either by training general practitioners or directly at the individual level.
Clustering; family practice; general practice; impaired fasting glucose; impaired glucose tolerance; intervention studies; risk management; type 2 diabetes
OBJECTIVE—We assessed the effects of a 2-day in-hospital diabetes educational program in preventing or delaying progression of impaired glucose tolerance (IGT) to type 2 diabetes, including analysis of changes in serum lipids, body weight, and blood pressure after the program.
RESEARCH DESIGN AND METHODS—A total of 426 subjects (51 ± 9 years, BMI 24.6 ± 3.9 kg/m2) with newly diagnosed IGT were randomly assigned to three groups, 143 as the short-term hospitalization with diabetes education and support (STH) group, 141 as the nonhospitalization but diabetes education and support (DES) group, and 142 as the neither hospitalization nor education (control) group.
RESULTS—The average follow-up was 3.1 years. The incidence of diabetes was 8.0, 10.7, and 13.2 cases per 100 person-years for STH, DES, and control groups, respectively. The incidence of diabetes was 42% lower (95% CI 33–51%) in the STH group and 27% lower (15–37%) in the DES group than in the control group. The incidence of diabetes was 21% lower (10–31%) in the STH group than in the DES group.
CONCLUSIONS—The 2-day in-hospital program with diabetes education and support every 3 months was more effective in preventing or delaying the progression from IGT to diabetes than only diabetes education and support every 3 months.
The purpose of this study was to evaluate the efficacy and feasibility of a newly developed diabetes patient education program consisting of a three-day hospitalization and a six-month follow-up by telephone counseling for patients with mild type 2 diabetes or impaired glucose tolerance (IGT) by a randomized controlled trial (RCT) method. Fifty-two patients with mild type 2 diabetes or IGT (HbAlc<8) were randomly assigned to either an intervention group or a control group. The current care was continued for the control group and the new education program was provided in addition to the current care for the intervention group. Changes in weight, blood glucose in a 75g-oral glucose tolerance test (75g-OGTT), and HbAlc were measured in June 1997 as baseline data and again in Dec. 1997. Scores for knowledge of diabetes, dietary habits, physical activity, health practice index, diabetes quality of life (DQOL), and self-efficacy were also obtained. After six months, the intervention group showed a statistically significant weight loss and blood glucose reduction in the 75g-OGTT test, but the control group did not. A significant improvement in lifestyle was observed in the intervention group, especially in terms of dietary habits and physical activity. The knowledge test scores increased in both groups. There were no significant differences in HbAlc, DQOL, or self-efficacy between the two groups. The results of this study show that the combination of a three-day hospitalization and a six-month follow-up by telephone counseling is effective in metabolic control and improvement of lifestyle for patients with mild type 2 diabetes or IGT. The reasons for the effectiveness were considered to be that l)changes in lifestyle were based on autonomous decision-making; 2)regular, consistent counseling was provided by the nurse in charge of each patient; 3)extended follow-up is more effective than initial education in preventing a rebound of weight or metabolic control.
randomized controlled trial; type 2 diabetes; IGT; patient education; telephone counseling
An International Expert Committee made recommendations for using the hemoglobin A1C (A1C) assay as the preferred method for diagnosis of diabetes in nonpregnant individuals. A concentration of ≥ 6.5% was considered as diagnostic. It is the aim of this study to compare the sensitivity of A1C with that of plasma glucose concentrations in subjects with early diabetes or IGT. We chose two groups of subjects who had A1C of ≤ 6.4%. The first group of 89 subjects had family histories of diabetes (MODY or T2DM) and had OGTT and A1C determinations. They included 36 subjects with diabetes or IGT and 53 with normal OGTT. The second group of 58 subjects was screened for diabetes in our Diabetes Clinic by FPG or 2HPG or OGTT and A1C and similar comparisons were made. Subjects with diabetes or IGT, including those with fasting hyperglycemia, had A1C ranging from 5.0 – 6.4%, mean 5.8%. The subjects with normal OGTT had A1C of 4.2 – 6.3%, mean 5.4% or 5.5% for the two groups. A1C may be in the normal range in subjects with diabetes or IGT, including those with fasting hyperglycemia. Approximately one third of subjects with early diabetes and IGT have A1C <5.7%, the cut-point that ADA recommends as indicating the onset of risk of developing diabetes in the future. The results of our study are similar to those obtained by a large Dutch epidemiological study. If our aim is to recognize early diabetic states to apply effective prophylactic procedures to prevent or delay progression to more severe diabetes, A1C is not sufficiently sensitive or reliable for diagnosis of diabetes or IGT. A combination of A1C and plasma glucose determinations, where necessary, are recommended for diagnosis or screening of diabetes or IGT.
Hemoglobin A1C; Diagnosis; Diabetes
Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as pre-diabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglycerides, HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program.
RESEARCH DESIGN AND METHODS
A total of 3,234 participants with impaired glucose tolerance (IGT) were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin, or placebo. Using repeated-measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status.
CVD risk factor values and changes from baseline became more unfavorable as glucose tolerance status deteriorated but improved with reversion to normal glucose tolerance (NGT), especially in the ILS intervention group (trend test P < 0.001 for all risk factors except for LDL PPD [P = 0.02] in ILS and HDL cholesterol [P = 0.02] in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia.
Progression from IGT to diabetes is associated with mild deterioration, whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS, but less so with metformin, in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously.
To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.
RESEARCH DESIGN AND METHODS
This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).
The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.
The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
Type 2 diabetes is preceded by a symptom-free period of impaired glucose tolerance (IGT). Pancreatic B-cell function decreases as glucose intolerance develops. In many patients with IGT, fasting blood glucose is within normal limits and hyperglycaemia occurs only postprandially. We examined whether pancreatic B-cell function changes during acute hyperglycaemia induced by oral glucose loading.
We calculated the insulinogenic index (I.I.) as an indicator of pancreatic B-cell function and measured serum levels of thioredoxin, a marker of cellular redox state, and 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative stress, during a 75-g oral glucose tolerance test (OGTT) in 45 subjects [24 patients with normal glucose tolerance (NGT), 14 with IGT and seven with Type 2 diabetes].
Thioredoxin levels decreased after glucose loading [66.1 ± 23.7, *59.3 ± 22.4, *49.3 ± 21.2 and *37.7 ± 18.0 ng/mL, fasting (0 min) and at 30, 60 and 120 min, respectively; *P < 0.001 vs. fasting]. In contrast, concentrations of 8-OHdG peaked at 30 min and then gradually decreased (0.402 ± 0.123, *0.440 ± 0.120, †0.362 ± 0.119 and †0.355 ± 0.131 ng/mL, *P < 0.05 vs. fasting, †P < 0.01 vs. 30 min). The insulinogenic index correlated with the change in thioredoxin levels (r = 0.34, P < 0.05). However, there was no relationship with the change in 8-OHdG levels from 0 to 30 min.
Hyperglycaemia in response to oral glucose impairs pancreatic B-cell function with decreasing thioredoxin levels. The augmented oxidative stress induced by hyperglycaemia may affect the cellular redox state. These findings strongly suggest that repeated postprandial hyperglycaemia may play an important role in the development and progression of diabetes mellitus.
blood glucose; impaired glucose tolerance; oxidative stress; postprandial hyperglycaemia
To verify whether the leptin gene epigenetic (DNA methylation) profile is altered in the offspring of mothers with gestational impaired glucose tolerance (IGT).
RESEARCH DESIGN AND METHODS
Placental tissues and maternal and cord blood samples were obtained from 48 women at term including 23 subjects with gestational IGT. Leptin DNA methylation, gene expression levels, and circulating concentration were measured using the Sequenom EpiTYPER system, quantitative real-time RT-PCR, and enzyme-linked immunosorbent assay, respectively. IGT was assessed after a 75-g oral glucose tolerance test (OGTT) at 24–28 weeks of gestation.
We have shown that placental leptin gene DNA methylation levels were correlated with glucose levels (2-h post-OGTT) in women with IGT (fetal side: ρ = −0.44, P ≤ 0.05; maternal side: ρ = 0.53, P ≤ 0.01) and with decreased leptin gene expression (n = 48; ρ ≥ −0.30, P ≤ 0.05) in the whole cohort. Placental leptin mRNA levels accounted for 16% of the variance in maternal circulating leptin concentration (P < 0.05).
IGT during pregnancy was associated with leptin gene DNA methylation adaptations with potential functional impacts. These epigenetic changes provide novel mechanisms that could contribute to explaining the detrimental health effects associated with fetal programming, such as long-term increased risk of developing obesity and type 2 diabetes.
To assess whether an increased genetic predisposition for type 2 diabetes (T2DM) influences the contributions of insulin resistance and impaired insulin secretion to impaired glucose tolerance (IGT), 437 subjects not known to have T2DM underwent an OGTT and a 3-hour hyperglycemic clamp. Plasma insulin responses and insulin sensitivity were compared between all subjects (unselected for demographic or anthropometric characteristics) that had normal glucose homeostasis and no first degree T2DM relative (NGH; N=133), IGT with a first degree T2DM relative (IGT/FH+; N=74) or IGT without a first degree T2DM relative (IGT/FH−; N=50). Compared to NGH, first and second phase plasma insulin responses were reduced ~45% and 30%, respectively (both P<0.001) in IGT/FH+, whereas insulin sensitivity was only ~20% reduced (P=0.011). In contrast, in IGT/FH−, first phase plasma insulin responses were only ~20% reduced (P=0.016), second phase plasma insulin responses were not reduced, but insulin sensitivity was ~40% reduced (P<0.001). IGT/FH+ differed significantly from IGT/FH− by having 25–30% lower first phase plasma insulin responses (P=0.026) and 25–30% greater insulin sensitivity (P=0.027). Adjustment for obesity abolished the differences in insulin resistance but not plasma insulin responses. However, when the IGT groups were stratified into subgroups based on body mass index (BMI), first phase plasma insulin responses were ~30% lower in IGT/FH+ with a BMI ≥27 kg/m2 (P=0.018) but similar in IGT/FH+ with a BMI <27 kg/m2 compared to the corresponding IGT/FH− subgroups. We conclude that in IGT an increased genetic predisposition for T2DM increases the contribution of impaired insulin secretion to its pathophysiology. This effect is enhanced by obesity.
impaired glucose tolerance; insulin resistance; insulin secretion
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.
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.
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.
The Diabetes Prevention Program (DPP) was a large, multicenter, randomized clinical trial testing interventions to prevent or delay type 2 diabetes. A major challenge was to identify eligible high-risk adults, defined by DPP as having both impaired glucose tolerance (IGT) (2-h glucose 140–199 mg/dl) and elevated fasting plasma glucose (EFG) (95–125 mg/dl).
RESEARCH DESIGN AND METHODS
We analyzed how screening yields would be affected by the presence of established risk factors such as age, sex, ethnicity, BMI, and family history of diabetes, and how much yields would be enhanced by preselecting individuals with elevated capillary blood glucose levels. Of 158,177 contacted adults, 79,190 were potentially eligible (no history of diabetes, age 25 years and older, BMI ≥ 24 kg/m2). We focus on the 30,383 participants who completed an oral glucose tolerance test (OGTT).
Based on OGTT, 27% had IGT with EFG, meeting DPP eligibility criteria for being at high risk of diabetes, and 13% had previously undiagnosed diabetes based on OGTT. Older age and higher BMI increased yield of high-risk individuals and those with newly discovered diabetes in most ethnic groups (whites, African Americans, Hispanics, and American Indians). In Asian Americans, age but not BMI predicted high risk and diabetes. Independent of age and BMI, the preliminary fasting capillary glucose predicted screening yield in all ethnic groups, with an inverted-U pattern defining DPP eligibility alone (IGT-EFG) and a steep curvilinear pattern defining either IGT-EFG or newly discovered diabetes. Fasting capillary glucose did not attenuate the affects of other participant characteristics in predicting IGT-EFG or the combination of IGT-EFG and newly discovered diabetes.
The DPP screening approach identified adults with or at high risk for type 2 diabetes across various ethnic groups and provided guidance to more efficient use of OGTTs. Fasting capillary glucose is a useful adjunct in screening programs combined with data on age and adiposity.
ADA, American Diabetes Association; CBL, Central Biochemistry Laboratory; DPP, Diabetes Prevention Program; EFG, elevated fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test
Increased fasting plasma glucose (FPG), which includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes, is a risk factor for arterial stiffness. While IFG is widely accepted as a cardiovascular risk factor, recent studies have argued that subjects with high-normal glucose level were characterized by a high incidence of cardiovascular disease. The purpose of this study is to investigate the relationship between FPG and arterial stiffness in non-diabetic healthy subjects.
We recruited 697 subjects who visited the health promotion center of a university hospital from May 2007 to August 2008. Age, sex, body mass index (BMI), resting heart rate, smoking habits, alcohol intake, exercise, blood pressure, medical history, FPG, lipid profile, high sensitivity C-reactive protein (hs-CRP), and Brachial-ankle pulse wave velocity (ba-PWV) were measured. We performed correlation and multiple linear regression analyses to divide the research subjects into quartiles: Q1(n = 172), 65 mg/dL ≤FPG < 84 mg/dL; Q2(n = 188), 84 mg/dL ≤FPG < 91 mg/dl; Q3(n = 199), 91 mg/dL ≤FPG < 100 mg/dL; Q4(n = 138), 100 mg/dL ≤FPG < 126 mg/dL.
FPG has an independent, positive association with ba-PWV in non-diabetic subjects after correcting for confounding variables, including age, sex, BMI, blood pressure, resting heart rate, hs-CRP, lipid profile, and behavioral habits. The mean ba-PWV of the high-normal glucose group (Q3, 1384 cm/s) was higher than that of the low-normal glucose group (1303 ± 196 cm/s vs.1328 ± 167 cm/s, P < 0.05). The mean ba-PWV value in the IFG group (1469 ± 220 cm/s) was higher than that in the normoglycemic group (P < 0.05, respectively).
An increase in FPG, even within the normal range, was associated with aggravated arterial stiffness. Further research is needed to determine the glycemic target value for the prevention of arterial stiffness in clinical and public health settings.
The Diabetes Prevention Program demonstrated the ability to delay or prevent type 2 diabetes in participants with impaired glucose tolerance (IGT). Participants with IGT are at high risk for cardiovascular disease (CVD), with a marked increase in the number and severity of CVD risk factors. We prospectively assessed the impact of our interventions on hypertension, dyslipidemia, and CVD events.
RESEARCH DESIGN AND METHODS
The study group consisted of 3,234 individuals with IGT randomly assigned to receive intensive lifestyle intervention, metformin, or placebo. Annual assessment of blood pressure, lipids, electrocardiogram, and CVD events was undertaken.
Hypertension was present in 30% of participants at study entry and then increased in the placebo and metformin groups, although it significantly decreased with intensive lifestyle intervention. Triglyceride levels fell in all treatment groups, but fell significantly more with intensive lifestyle intervention. Total cholesterol and LDL cholesterol levels were similar among treatment groups. Intensive lifestyle intervention significantly increased the HDL cholesterol level and reduced the cumulative incidence of the proatherogenic LDL phenotype B. At 3 years of follow-up, the use for pharmacologic therapy to achieve established goals in the intensive lifestyle group was 27–28% less for hypertension and 25% less for hyperlipidemia compared with placebo and metformin groups. Over an average of 3 years, 89 CVD events from 64 participants were positively adjudicated studywide, with no differences among treatment groups.
Lifestyle intervention improves CVD risk factor status compared with placebo and metformin therapy. Although no differences in CVD events were noted after 3 years, achieved risk factor modifications suggest that longer intervention may reduce CVD event rates.
ATP, Adult Treatment Panel; CVD, cardiovascular disease; DPP, The Diabetes Prevention Program; ECG, electrocardiogram; IGT, impaired glucose tolerance; NHANES, National Health and Nutrition Examination Survey
A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized.
Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group.
After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027).
The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention.
Trial registration number
Haematopoietic stem cells undergo mobilization from bone marrow to blood in response to physiological stimuli such as ischemia and tissue injury. The aim of study was to determine the kinetics of circulating CD34+ and CD133+CD34+ progenitor cells in response to 75 g glucose load in subjects with normal and impaired glucose metabolism.
Asian Indian male subjects (n = 50) with no prior history of glucose imbalance were subjected to 2 hour oral glucose tolerance test (OGTT). 24 subjects had normal glucose tolerance (NGT), 17 subjects had impaired glucose tolerance (IGT) and 9 had impaired fasting glucose (IFG). The IGT and IFG subjects were grouped together as pre-diabetes group (n = 26). Progenitor cell counts in peripheral circulation at fasting and 2 hour post glucose challenge were measured using direct two-color flow cytometry.
The pre-diabetes group was more insulin resistant (p < 0.0001) as measured by homeostasis assessment model (HOMA-IR) compared to NGT group. A 2.5-fold increase in CD34+ cells (p = 0.003) and CD133+CD34+ (p = 0.019) cells was seen 2 hours post glucose challenge in the NGT group. This increase for both the cell types was attenuated in subjects with IGT. CD34+ cell counts in response to glucose challenge inversely correlated with neutrophil counts (ρ = -0.330, p = 0.019), while post load counts of CD133+CD34+ cells inversely correlated with serum creatinine (ρ = -0.312, p = 0.023).
There is a 2.5-fold increase in the circulating levels of haematopoietic stem cells in response to glucose challenge in healthy Asian Indian male subjects which is attenuated in subjects with pre-diabetes.
Central arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study.
The study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined.
Among studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise.
Elevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.
Pre-diabetes; ADMA; Pulse wave velocity; Endothelial progenitor cells
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.
β cell function; insulin resistance; insulin sensitivity; newly-diagnosed diabetes mellitus; pre-diabetes; total glucagon-like peptide-1.
Background and Objectives
The aim of the present study was to evaluate left ventricle systolic and diastolic function, using tissue Doppler echocardiography (TDE), in relation to blood glucose status in prediabetic patients who had no evidence of heart disease by conventional echocardiography (CE).
Subjects and Methods
We included 60 patients (30 female, 30 male) and 20 healthy controls (10 male, 10 female). All participants were randomised into four groups according to their oral glucose tolerance test. Group-I consisted of those patients who had only impaired fasting glucose (IFG). group-II consisted of patients who had only impaired glucose tolerance (IGT) and group-III consisted of patients who had both IFG and IGT, that is so-called combined glucose intolerance. Group-IV included the healthy controls. All subjects underwent both CE and TDE.
No significant differences were found among the four groups in terms of CE. There was no significant difference between group-IV and group-I with respect to the early peak diastolic velocity (Ea) of medial mitral annulus (11.65±0.66 vs. 9.72±1.58, p>0.05), whereas a statistically significant difference was found between group-IV and group-II (11.65±0.66 vs. 9.06±1.07, p<0.001) and between group-IV and group-III (11.65±0.66 vs. 9.74±1.09, p<0.05).
Diastolic myocardial dysfunction in prediabetic patients may be identified by quantitative TDE before the appearance of CE indices of myocardial dysfunction.
Type 2 diabetes mellitus; Diabetic cardiomyopathies; Tissue Doppler imaging; Glucose intolerance
We aimed to investigate the influence of positive family history (FH+) of diabetes and 19 known genetic risk loci on the effectiveness of lifestyle changes and their predictive value on the incidence of type 2 diabetes in the Finnish Diabetes Prevention Study (DPS).
RESEARCH DESIGN AND METHODS
A total of 522 subjects with impaired glucose tolerance (IGT) were randomized into the control (n = 257) and intervention (n = 265) groups. The mean follow-up was 6.2 years (median 7 years), and the lifestyle intervention, aimed at weight reduction, healthy diet, and increased physical activity, lasted for 4 years (range 1–6 years). An oral glucose tolerance test (OGTT) and assessment of basic clinical variables were performed annually.
The effect of intervention on the incidence of diabetes was almost similar in subjects with FH+ compared with subjects with a negative family history (FH−) of diabetes during the entire follow-up. In the Cox model, including FH, genetic risk SNPs, and randomization group, and adjusted for the effects of age, sex, BMI, and study center, only lifestyle intervention had a significant effect (hazard ratio 0.55, 95% CI 0.41–0.75, P < 0.001) on the incidence of diabetes. Further analyses showed that in addition to the baseline glucose and insulin values, 1-year changes in 2-h glucose and 2-h insulin achieved by lifestyle intervention had a significant effect on the incidence of diabetes.
These results emphasize the effectiveness of lifestyle intervention in reducing the risk of diabetes in high-risk individuals independently of genetic or familial risk of type 2 diabetes.