The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1)

Aims/hypothesis Lifestyle modification helps in the primary prevention of diabetes in multiethnic American, Finnish and Chinese populations. In a prospective community-based study, we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger, leaner and more insulin resistant than the above populations. Methods We randomised 531 (421 men 110 women) subjects with IGT (mean age 45.9±5.7 years, BMI 25.8±3.5 kg/m²) into four groups. Group 1 was the control, Group 2 was given advice on lifestyle modification (LSM), Group 3 was treated with metformin (MET) and Group 4 was given LSM plus MET. The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria. Results The median follow-up period was 30 months, and the 3-year cumulative incidences of diabetes were 55.0%, 39.3%, 40.5% and 39.5% in Groups 1–4, respectively. The relative risk reduction was 28.5% with LSM (95% CI 20.5–37.3, p=0.018), 26.4% with MET (95% CI 19.1–35.1, p=0.029) and 28.2% with LSM + MET (95% CI 20.3–37.0, p=0.022), as compared with the control group. The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM, 6.9 for MET and 6.5 for LSM + MET. Conclusions/interpretation Progression of IGT to diabetes is high in native Asian Indians. Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT; there was no added benefit from combining them. Electronic Supplementary Material Supplementary material is available for this article at     

Serum immunoreactive insulin responses to a glucose load in Asian Indian and European Type 2 (non-insulin-dependent) diabetic patients and control subjects

Summary The serum immunoreactive insulin response to an oral glucose load was estimated in 15 Asian Indian and 29 European non-diabetic subjects, and in 45 Asian Indian and 72 European Type 2 (non-insulin-dependent) diabetic patients. In the non-diabetic group, basal insulin values were higher in the Asian Indians than the Europeans (16.7 ± 3.0 vs. 6.9 ± 0.7 mU/l, p < 0.001), and remained higher throughout the glucose tolerance test. Total insulin response was also higher in the Asian Indians (p < 0.001), and linear regression analysis revealed basal insulin, body mass index and race to be important predictors of insulin response. Amongst the diabetic patients, basal insulin values were again higher in the Asian Indians compared with the Europeans (18.0±5.0 vs. 11.5±0.9 mU/l, p<0.05). Total insulin response was also greater (p < 0.01). Linear regression analysis revealed the basal insulin value to be the only significant predictor of insulin response. The results demonstrate higher insulin levels in Asian Indians than Europeans in both normal subjects and Type 2 diabetic subjects. The insulin response to a glucose load is also greater in the Asian Indians. In the control subjects, ethnic differences contribute to this response, whereas in the diabetic patients this is a function of the elevated basal insulin values of the Asian Indians.     

The Relationship Between Obesity,Plasma Immunoreactive Insulin Concentration and Blood Pressure in Newly Diagnosed Indian Type 2 Diabetic Patients

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24–59) years, IGT 48 (29–64) years, diabetic 43 (29–60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m^?2 (17.2–29.9), IGT 26.0 kg m^?2 (19.8–33.9), diabetic 24.2 kg m^?2 (19.3–32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70–0.98), IGT 0.88 (0.75–0.98), diabetic 0.89 (0.75–1.00)). Blood pressure was significantly higher in both IGT (systolic 127mmHg (108–162), diastolic 80 mmHg (66–99)) and diabetic patients (systolic 130 mmHg (104–160), diastolic 84 mmHg (66–102)) compared to non-diabetic controls (systolic 120 mmHg (100–151), diastolic 80 mmHg (60–94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r= 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r= ? 0.25, p<0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r= 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r= 0.30, p < 0.001, post glucose r = ? 0.20, p < 0.05) but not to C-peptide concentrations. Multivariate analysis revealed that systolic blood pressure in diabetic patients was related to BMI (p < 0.01) and fasting immunoreactive insulin (p < 0.05) while diastolic blood pressure was related to BMI (p < 0.001) and waist-hip ratio (p < 0.01). Thus, blood pressure is associated with obesity even in our relatively non-obese population and it is also associated with plasma immunoreactive insulin concentrations. The mechanism of these associations remains to be established.     

Proton magnetic resonance spectroscopy study of soleus muscle in non-obese healthy and Type 2 diabetic Asian Northern Indian males: high intramyocellular lipid content correlates with excess body fat and abdominal obesity.

AIMS: Intramyocellular lipids (IMCL) appears to be important in the pathogenesis of insulin resistance. Correlation of IMCL content of soleus muscle with insulin sensitivity has been reported in the Caucasian population. In the present study, IMCL content was estimated in the soleus muscle of both non-obese healthy males and Type 2 diabetic males, and correlated with the anthropometric parameters, blood glucose, plasma lipids, and insulin resistance in Asian Indians from North India. METHODS: Twenty males (Type 2 diabetes mellitus 10; healthy controls 10) with body mass index (BMI) 25. The following were assessed in all subjects: body composition, fasting blood glucose, lipid profile, insulin levels, insulin resistance by homeostasis model assessment, and proton magnetic resonance spectroscopy (1H MRS) study of the soleus muscle. RESULTS: IMCL content was approximately two times higher in Type 2 diabetic males compared with healthy males (P < 0.05). Amongst healthy males, IMCL content was significantly higher (P < 0.05) in subjects with percentage BF > 25 compared with subjects with percentage BF or= 25. Similarly, IMCL content was high in subjects with waist-hip ratio (WHR) > 0.95 compared with subjects with WHR 相似文献   

Undiagnosed Glucose Intolerance in the Community: the Isle of Ely Diabetes Project

The Isle of Ely Diabetes Project is a prospective population-based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist-hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL-cholesterol, but not total or LDL-cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized β coefficient = -0.12, p<0.01).     

Serum Total Adiponectin Is Associated with Impaired Glucose Tolerance in Asian Indian Females but Not in Males

Objective

Adiponectin may play a role in the development of type 2 diabetes and cardiovascular disease (CVD). However, little is known about the relationship between adiponectin and impaired glucose tolerance (IGT). We investigated the association between adiponectin and IGT and between adiponectin and cardiovascular risk factors among subjects with IGT.

Research Design and Methods

Subjects with normal glucose tolerance (NGT)(n = 571) and impaired glucose tolerance (n = 167) were recruited from the Chennai Urban Rural Epidemiology Study in south India. Serum total adiponectin levels were measured using a radioimmunoassay (Linco Research, St. Charles, MO). High sensitivity C-reactive protein (hsCRP) was estimated by nephelometry.

Results

In sex-stratified analyses, adiponectin was significantly associated with IGT in females [odds ratio (OR): 0.93, 95% confidence interval (CI): 0.872–0.991, p = 0.026] after controlling for age, waist circumference, blood pressure, alcohol consumption, smoking, lipid profile, and glycemic indices; in males there was no significant association (OR = 0.90, 95% CI: 0.798–1.012, p = 0.078). In prediabetic females, adiponectin was not associated with any CVD risk factors (age, waist circumference, blood pressure, cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, fasting glucose, fasting insulin, and insulin resistance level), but was associated negatively with 2-hour postplasma glucose levels (r = –0.243, p < 0.05) and hsCRP (r = –0.219, p < 0.05) after adjusting for demographic and biomedical indices. No associations with CVD risk factors were observed in males with IGT.

Conclusion

Serum total adiponectin levels are associated with IGT, 2-hour postplasma glucose, and hsCRP in Asian Indian females but not in males.     

肥胖者胰岛素分泌功能对糖耐量低减及糖尿病发生的影响

目的　探讨肥胖者胰岛素分泌变化对糖耐量低减 (IGT)及糖尿病 (DM)发生的影响。　方法　对 30例单纯性肥胖 [体重指数 (BMI) >2 7]患者进行血糖和胰岛素测定 ,并观察胰岛细胞分泌指数 (HOMA- IS)及胰岛素敏感性指数 (IAI) ,并对这些患者进行 15年随访。　结果　肥胖者空腹胰岛素 (FINS)水平明显高于正常人 (P <0 .0 1) ,与 HOMA - IS明显的正相关 (P <0 .0 1) ;空腹血糖(FPG)与 HOMA- IS及 IAI呈明显的负相关 (P<0 .0 1)。15年内 6 3.3%的肥胖者发展成 IGT,5 0 .0 %的肥胖者及发展成 IGT者发展为 2型 DM。　结论　肥胖对 IGT及糖尿病的发生、发展有着明显的影响 ,控制体重是减少 IGT发生的重要环节。     

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial

Background/objectives

The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140–199 mg/dL at 120 min (IGT-A) or PG levels 140–199 mg/dL at 120 min and >200 mg/dL at 30/60/90 min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D).

Insulin secretion and action in different stages of glucose tolerance in Asian Indians.

AIMS: To evaluate the sequence of changes in insulin secretion and action in different stages of glucose tolerance and the effect of obesity on insulin profile in South Indian adults. Blood samples from 260 consecutive cases with no known history of diabetes were collected. Plasma insulin levels were measured during a 75-g oral glucose tolerance test. Insulin resistance (IR) was calculated, using the homeostasis model assessment (HOMA). An index of insulin secretion was derived as the ratio of incremental insulin at 30 min divided by 30 minute plasma glucose (delta I/G). RESULTS: Normoglycaemia was present in 164, impaired glucose tolerance (IGT) in 60 and diabetes in 36 subjects. Fasting and 2 h insulin secretion showed bell shaped curves with increasing plasma glucose. The peak values corresponded to the cut-off values used for the diagnosis of clinical diabetes. IR was higher in obese than in nonobese, nondiabetic subjects but the effect of obesity on IR was not found in subjects with diabetes. IGT was associated with higher IR, but not with evidence of a beta-cell defect. CONCLUSIONS: Evaluation of insulin resistance and beta-cell function in different stages of glucose tolerance indicate that insulin resistance is manifested in the early stage of glucose intolerance in South Indians, i.e. IGT. A beta-cell defect was mostly found in people with diabetes. The beta-cell defect is more common in diabetes among the nonobese.     

Distinguishing between persistent and transient impaired glucose tolerance using a prediction model.

Screening for impaired glucose tolerance (IGT) and Type 2 (non-insulin dependent) diabetes was carried out in 777 people and those with high blood glucose levels completed three 2-h oral glucose tolerance tests (OGTT). Blood lipid levels, fasting and 2-h insulin levels, body mass index, and blood pressure were also measured and family history of Type 2 diabetes recorded. Fifty people were identified with IGT and of these 21 were found to have persistent IGT and 29 transient IGT. A model including the variables body mass index, fasting and 2-h insulin levels, fasting triglycerides and family history of Type 2 diabetes was developed using the Speigelhalter-Knill-Jones weighting method to predict subjects with persistent IGT. This model could be useful in identifying people with persistent IGT and therefore eliminate the need for repeat OGTTs which are time consuming and expensive.     

2型糖尿病预防的药物与非药物干预循证医学研究进展

糖耐量减低(IGT)、空腹血糖受损(IFG)是正常糖代谢发展到糖尿病的一个过渡阶段,与糖尿病的发牛密切相关.研究表明,对此类人群给予药物、非药物干预可以明显减少2型糖尿病的发生,具有重要的临床意义.本文就2型糖尿病的药物与非药物干预的相关研究作一综述.     

Oral contraceptive use and abnormal glucose regulation in Swedish middle aged women

Aim

To investigate the association between oral contraceptive (OC) use and abnormal glucose regulation in Swedish middle aged women.

Methods

A prospective population-based study including 4794 women, aged 36-56 at baseline. None had previously diagnosed diabetes. At both baseline and follow-up 8 years later, the women were examined by oral glucose tolerance test. Information regarding lifestyle factors and anthropometric measurements were collected.

Results

At baseline, current use of OCs was associated with pre (Odds ratio, OR 4.1, 95%CI 2.2-7.8) but not with type 2 diabetes. The association to prediabetes was entirely linked to IGT (OR 7.1, 3.3-15.8) in current users of OCs and in former users (OR 2.1, 1.1-3.9). Women who used OC at baseline had a better cardiovascular disease risk profile; lower body mass index (BMI), more physically active and less smoking. At follow-up, the increased risk did not persist.

Conclusion

Current use of OC was associated with a four times increased risk of having prediabetes and seven times of having impaired glucose tolerance. No increased risk persisted at the follow-up, suggesting that the risk due to prior use of OC is decreasing with time. The healthier lifestyle in women who used OCs may have contributed to reduced long-term risk of prediabetes.     

Determinants of the progression to type 2 diabetes and regression to normoglycemia in people with pre-diabetes: A population‐based cohort study over ten years

AimsTo determine the rates and predictors of the regression to normoglycemia and progression to diabetes among subjects with pre-diabetes.MethodsA 10-year longitudinal population-based study was conducted among 1329 participants with pre-diabetes in the Tehran Lipid and Glucose Study. Pre-diabetes was divided into isolated IFG (iIFG), isolated IGT (iIGT), and combined IFG/IGT. Univariate and stepwise multivariable Cox regression was used to evaluate predictors of glycemic conversions.ResultsThe cumulative incidences of normoglycemia and diabetes were 43.7% (95%CI 40.9–46.4) and 40.1% (37.3–42.7), respectively. Isolated IGT returned to normoglycemia more than iIFG (HR:1.26, 1.05–1.51), but there was no difference in how quickly they progressed to diabetes. Regression to normoglycemia was associated with younger age, female sex, lower BMI, no familial history of diabetes, higher HDL-C, and ex-smoking. Older age, higher BMI, diastolic blood pressure, total cholesterol, lower HDL-C, and familial history for diabetes were associated with progression to diabetes. The influence of BMI on glycemic status conversions diminished with age. At approximately above 60 years old, the hazards of BMI for any conversions faded out.ConclusionsThe modifiable predictors of regression to normoglycemia and progression to diabetes are roughly the same. The importance of BMI attenuates in elderly subjects.     

Telomere shortening occurs in Asian Indian Type 2 diabetic patients.

AIM: Telomere shortening has been reported in several diseases including atherosclerosis and Type 1 diabetes. Asian Indians have an increased predilection for Type 2 diabetes and premature coronary artery disease. The aim of this study was to determine whether telomeric shortening occurs in Asian Indian Type 2 diabetic patients. METHODS: Using Southern-blot analysis we determined mean terminal restriction fragment (TRF) length, a measure of average telomere size, in leucocyte DNA. Type 2 diabetic patients without any diabetes-related complications (n = 40) and age- and sex-matched control non-diabetic subjects (n = 40) were selected from the Chennai Urban Rural Epidemiology Study (CURES). Plasma level of malondialdehyde (MDA), a marker of lipid peroxidation, was measured by TBARS (thiobarbituric acid reactive substances) using a fluorescence method. RESULTS: Mean (+/- SE) TRF lengths of the Type 2 diabetic patients (6.01 +/- 0.2 kb) were significantly shorter than those of the control subjects (9.11 +/- 0.6 kb) (P = 0.0001). Among the biochemical parameters, only levels of TBARS showed a negative correlation with shortened telomeres in the diabetic subjects (r = -0.36; P = 0.02). However, telomere lengths were negatively correlated with insulin resistance (HOMA-IR) (r = -0.4; P = 0.01) and age (r = -0.3; P = 0.058) and positively correlated with HDL levels (r = 0.4; P = 0.01) in the control subjects. Multiple linear regression (MLR) analysis revealed diabetes to be significantly (P < 0.0001) associated with shortening of TRF lengths. CONCLUSIONS: Telomere shortening occurs in Asian Indian Type 2 diabetic patients.     

流式细胞仪检测外周血单核细胞核因子-κB在糖耐量减低中的表达及意义

目的了解糖耐量减低患者外周血单核细胞核因子-κB表达,探讨其与糖耐量减低发生发展的关系。方法检测正常对照组（NGT,20例）、糖耐量减低组（IGT,20例）,采用流式细胞仪检测两组人群外周血单核细胞（PMNC）中核因子κB（NF—κB）的表达水平,同时测定空腹血清胰岛素（FINS）、血糖（FBS）浓度及血脂,计算胰岛素抵抗指数（HOMA-IR）和胰岛β细胞分泌指数。结果IGT组外周血单核细胞中核因子κB表达为11．57±4．01,显著高于NGT组3．98±2．16（P〈0．05）;相关分析显示NF-κB的表达水平与HOMA—IR呈正相关。结论IGT患者外周血单核细胞中NF—κB的表达增高,显示IGT体内存在低度炎症反应,其可能参与胰岛素抵抗及糖耐量减低的发生及发展。     

Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians

Background

We estimated the prevalence of metabolically obese nonobese (MONO), metabolically obese obese (MOO), and metabolically healthy obese (MHO) individuals and correlated this with the prevalence of coronary artery disease (CAD) compared to metabolically healthy nonobese (MHNO) in urban South Indians.

Method

Study subjects (n = 2350) were recruited from the Chennai Urban Rural Epidemiology Study. Generalized obesity was defined as a body mass index (BMI) ≥25 kg/m², based on the World Health Organization Asia Pacific guidelines. Metabolic syndrome (MS) was diagnosed based on the South Asian Modified-National Cholesterol Education Programme criteria. Coronary artery disease was defined by known myocardial infarction or Q waves on resting electrocardiogram.

Results

Metabolically obese nonobese was defined as nonobese subjects (BMI < 25 kg/m²) with MS, MOO as obesity (BMI ≥ 25 kg/m²) with MS, MHO as obese subjects (BMI ≥ 25 kg/m²) with no MS, and MHNO as no obesity or MS. Metabolically obese nonobese was identified in 355 (15.1%), MOO in 348 (14.8%), MHO in 312 (13.3%), and MHNO in 1335 (56.8%) subjects. The prevalence of CAD among the MONO, MOO, MHO, and MHNO was 5.5%, 4.2%, 1.4%, and 2.6%. However, when age standardization was done, there was no statistically significant increase in the risk of CAD among MONO [odds ratio (OR) = 1.300, 95% confidence interval (CI) 0.706–2.394, p = .339], MOO (OR = 1.651, 95% CI 0.852–3.199, p = .137), and MHO (OR = 0.524, 95% CI 0.250–2.130, p = .564) groups compared to MHNO, perhaps due to small numbers.

Conclusion

Metabolic obesity may have different clinical implications than phenotypic obesity.     

Polynesians: prone to obesity and Type 2 diabetes mellitus but not hyperinsulinaemia.

AIMS: To compare the extent of hyperinsulinaemia among New Zealand Europeans and Polynesians (an ethnic group at high risk of Type 2 diabetes mellitus). METHODS: A cross-sectional survey from randomly selected households was conducted in inner urban South Auckland. Subjects were either European, Maori or Pacific Islands Polynesians aged 40-79 years and were screened for diabetes using a random blood glucose. Those with an elevated result, and 20% randomly selected from those with a normal screening result, were invited to a 75-g glucose tolerance test. WHO criteria (1998) for diabetes were used. RESULTS: In those aged 40-59 years, total prevalence of diabetes was 7.5 (6.2-9.0)% in Europeans but 21.1 (16.6-25.6)% among Maori and 25.0 (19.8-30.1)% among Pacific peoples; obesity (body mass index >or= 31.0 kg/m2) was present in 26% Europeans, 63% Maori and 69% Pacific peoples. Non-diabetic Polynesians were relatively hyperglycaemic and hyperinsulinaemic. After adjusting for the degree of obesity, Polynesians had similar insulin levels to Europeans. CONCLUSIONS: These findings indicate that Polynesians are not intrinsically insulin resistant as a group, a prerequisite found in most other ethnic groups at high risk of Type 2 diabetes mellitus. The high prevalence of Type 2 diabetes in Polynesians could be the result of their high prevalence of obesity.     

Hyperglycaemic Progression in Subjects with Impaired Glucose Tolerance: Association with Decline in Beta Cell Function

Impaired glucose tolerance is associated with an increased risk of Type 2 diabetes. This prospective cohort study has examined the variables associated with hyperglycaemic progression in order to elucidate the aetiology of this deterioration. The 5 mg glucose-kg ideal body weight-min^?1 continuous infusion of glucose with model assessment (CIGMA) test was used to quantitate glucose tolerance, beta cell function, and insulin sensitivity. Twenty-two Caucasian subjects who had impaired glucose tolerance identified on two separate tests underwent repeat testing after a median period of 24 months. At follow-up, 2 of the 22 subjects (9%) had Type 2 diabetes, 18 (82%) had impaired glucose tolerance, and 2 (9%) were normoglycaemic. The fasting and achieved (60-min) glucose levels were significantly higher at follow-up (mean ± SD) (5.7 ± 0.8 vs 5.5 ± 0.5 mmol l^?1, p = 0.029 and 10.0 ± 0.9 vs 9.6 ± 0.6 mmol l^?1, p = 0.021, respectively), and beta cell function was significantly lower (median and interquartile range): 75% (50–93%) vs 90% (70–135%), p = 0.009. The changes in fasting plasma glucose were found to correlate with change in body mass index (r_s = 0.46, p = 0.03). We conclude that impaired glucose tolerance is associated with decline in beta cell function, and denotes substantial risk of hyperglycaemic progression. Randomized controlled trials are warranted to determine whether exercise programmes, dietary advice, and attentive follow-up and effective preventive strategies for subjects with impaired glucose tolerance.