Incidence of Type 2 diabetes in the elderly German population and the effect of clinical and lifestyle risk factors: KORA S4/F4 cohort study

Aims To determine the incidence of Type 2 diabetes in an elderly population in Germany and its association with clinical and lifestyle factors. Methods Oral glucose tolerance tests (OGTT, World Health Organization criteria) were carried out in a random sample of 1353 subjects (age group 55–74 years; 62% response) in Augsburg (Southern Germany) (1999–2001). The cohort was re‐investigated in 2006–2008. Of those individuals without diabetes (baseline), 887 (74%) participated in the follow‐up. Results Ninety‐three (10.5%) developed diabetes during the 7‐year follow‐up period {standardized incidence rates [95% confidence interval (CI)] per 1000 person‐years: total 15.5; 12.6, 19.1; men 20.2; 15.6, 26.1; women 11.3; 7.9, 16.1}. In both sexes, those who developed diabetes were slightly older, were more obese, had a more adverse metabolic profile (higher glucose values, HbA_1c, fasting insulin, uric acid, and triglycerides) and were more likely to have hypertension at baseline than were participants remaining free of diabetes (P < 0.05). On stepwise logistic regression, age, parental diabetes, body mass index, uric acid, current smoking, HbA_1c and fasting and 2‐h glucose (OGTT) were strong predictors of diabetes incidence. The risk of diabetes was higher in subjects with isolated impaired glucose tolerance (odds ratio 8.8; 95% CI 5.0, 15.6) than in isolated impaired fasting glucose (4.7; 2.2, 10.0), although the difference did not reach statistical significance. Conclusions For the first time, we have estimated the incidence of Type 2 diabetes in an elderly German cohort and demonstrated that it is among the highest in Europe. The OGTT appears to be useful in identifying individuals with high Type 2 diabetes risk. Our results support a role of smoking in the progression to diabetes.     

Fluctuations in HbA1c are associated with a higher incidence of cardiovascular disease in Japanese patients with type 2 diabetes

Aims/Introduction: To reveal whether visit‐to‐visit variability in HbA1c is associated with higher risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Materials and Methods: The study was conducted on 689 Japanese patients with type 2 diabetes [295 women, 394 men; mean (±standard deviations (SD)) age 65 ± 11 years]. Variability in HbA1c was evaluated as the intrapersonal SD of serial measurements of HbA1c during the follow‐up period for at least 12 months. Patients were divided into quartiles according to the SD of HbA1c, and the primary endpoint was defined as incident CVD. Cox’s proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During a median follow‐up period of 3.3 years (range 1.0–6.3 years), 26 ± 14 measurements of HbA1c were obtained per patient and 61 episodes of incident CVD were recorded. The 5‐year cumulative incidence of CVD in patients across the first, second, third, and fourth quartiles of SD in HbA1c was 4.9, 8.7, 17.1, and 26.2%, respectively (P < 0.001, log‐rank test). Multivariate Cox regression analysis revealed that the incidence of CVD was significantly higher in patients in the fourth quartile of SD in HbA1c compared with those in the first quartile (HR 3.38; 95% CI 1.07–10.63; P = 0.039), independent of mean HbA1c and other traditional cardiovascular risk factors. Conclusions: Variability of HbA1c may be a potent predictor of incident CVD in Japanese patients with type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00155.x, 2011)     

正常低浓度血镁与2型糖尿病的相关性研究

目的:探讨正常偏低浓度血镁与2型糖尿病的相关性。方法:2010年3月至7月对上海市嘉定区菊园新区2 515名40岁以上居民进行问卷调查,测量身高、体重、腰围、血压等,并进行口服葡萄糖耐量试验(OGTT),采血检测血清镁、胰岛素、肝功能、肾功能、空腹及OGTT 2 h血糖(2hPG)。分析人群血镁浓度与2型糖尿病患病风险的相关性。结果:①在血镁的参考范围内,2hPG、2 h胰岛素、总胆固醇、低密度脂蛋白胆固醇和三酰甘油在血镁四分位分组各组间差异有统计学意义(均趋势P<0.01);校正相关混杂因素后,3组2型糖尿病患病风险OR(95%CI)分别是1.11(0.75～1.66)、1.61(1.08～2.40)和3.22(2.23～4.64)(趋势P<0.01)。结论:上海郊区40岁以上人群中,正常的低血镁水平与2型糖尿病患病风险显著相关。     

The relative risks of hyperglycaemia, obesity and dyslipidaemia in the relatives of patients with Type II diabetes mellitus (Short Communication)

Summary Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by environmental factors. Although the familial aggregation of Type II diabetes is acknowledged, there is little data concerning the prevalence of diabetes in the relatives of subjects with diabetes in comparison with the general population, and our objective was to address this question in the defined geographic region of Oxfordshire, England. We studied 139 first degree relatives of 90 probands with Type II diabetes who attended routine diabetes clinics in Oxfordshire and documented the fasting plasma glucose, triglyceride and HDL-cholesterol concentrations and BMI of these subjects. The probands were selected without regard to family history of diabetes. The control population data were derived from two large-scale Oxford community studies which documented the prevalences of known and newly diagnosed diabetes. The prevalences of newly diagnosed and known diabetes were calculated for each group. The mean BMI, and concentrations of fasting glucose, triglyceride and HDL-cholesterol were compared and prevalence ratios for obesity (defined as BMI > 30 kg/m²), hyperglycaemia (defined as fasting plasma glucose ≥ 6.1 mmol/l), and dyslipidaemia (defined as triglyceride > 2.0 mmol/l, HDL < 1.0 mmol/l) were calculated. There was a fourfold higher prevalence of hyperglycaemia in the first degree relatives of subjects with Type II diabetes compared with the control population: the prevalence ratio after adjustment for age, sex and BMI was 4.32 (95 % confidence interval 2.29–8.17). The relatives had a considerably higher fasting plasma glucose concentration than the control population (5.18 ± 0.67 mmol/l (mean ± 1 SD) vs 4.76 ± 1.59 mmol/l, p = 0.0001), and this difference remained statistically significant after adjustment for age, sex and obesity. The relatives were significantly more obese, had higher fasting plasma insulin concentrations and had lower HDL-cholesterol concentrations. In conclusion, there is a strong familial aggregation of hyperglycaemia and obesity in the relatives of subjects with Type II diabetes and these subjects have higher fasting plasma insulin concentrations and lower HDL-cholesterol than the general population. These data indicate the particular relevance of screening the first degree relatives of subjects with Type II diabetes, as intervention strategies which aim to improve the metabolic profile are indicated for a large proportion of these subjects. [Diabetologia (1999) 42: 24–27] Received: 8 May 1998 and in revised form 31 July 1998     

Persistence of the effect of birth size on dysglycaemia and type 2 diabetes in old age: AGES-Reykjavik Study

We studied the effect of birth size on glucose and insulin metabolism among old non-diabetic individuals. We also explored the combined effect of birth size and midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised 1,682 Icelanders whose birth records included anthropometrical data. The same individuals had participated in the prospective population-based Reykjavik Study, where BMI was assessed at a mean age of 47 years, and in the AGES-Reykjavik Study during 2002 to 2006, where fasting glucose, insulin and HbA_1c were measured and homeostasis model assessment for the degree of insulin resistance (HOMA-IR) calculated at a mean age of 75.5 years. Type 2 diabetes was determined as having a history of diabetes, using glucose-modifying medication or fasting glucose of >7.0 mmol/l. Of the participants, 249 had prevalent type 2 diabetes in old age. Lower birth weight and body length were associated with higher fasting glucose, insulin, HOMA-IR and HbA_1c among old non-diabetic individuals. Higher birth weight and ponderal index at birth decreased the risk for type 2 diabetes in old age, odds ratio (OR), 0.61 [95 % confidence interval (CI), 0.48–0.79] and 0.96 (95 % CI, 0.92–1.00), respectively. Compared with those with high birth weight and low BMI in midlife, the odds of diabetes was almost five-fold for individuals with low birth weight and high BMI (OR, 4.93; 95 % CI, 2.14–11.37). Excessive weight gain in adulthood might be particularly detrimental to the health of old individuals with low birth weight.     

Larger body mass index and waist circumference are associated with lower mortality in Chinese long-term care facility residents

OBJECTIVES: To investigate the association between body mass index (BMI) and waist circumference (WC) and all‐cause mortality of Chinese residents in long‐term care facilities in Taiwan. DESIGN: Prospective cohort study. SETTING: Eight long‐term care facilities in Taiwan. PARTICIPANTS: Three hundred fifty‐four residents aged 60 and older (median 78.4, range 60–101; 156 men, 198 women) were recruited during the study period. MEASUREMENTS: Anthropometrics and metabolic parameters were measured at baseline. Mean BMI was 21.7±4.2 kg/m² (range 11.6–35.3 kg/m², and mean WC was 82.4±10.9 cm (range 55.0–124.0 cm). Mortality data were from the Department of Health in Taiwan. RESULTS: There were 219 deaths during the 5 years of follow‐up. After adjusting for age, sex, albumin, Karnofsky performance status scale, hypertension, and diabetes mellitus, subjects in the highest quartile of BMI (27.3± 2.8 kg/m²) and WC (96.7±7.4 cm) had a significantly lower mortality rate than did subjects in the lowest quartile (BMI, 16.7±1.7 kg/m²; WC, 69.6±4.2 cm). After further stratification according to central obesity status, the subjects in the two highest BMI quartiles had a lower mortality rate than those in the lowest BMI quartile but only in the central obesity group (≥90 cm in men or ≥80 cm in women). The adjusted relative risk for all‐cause mortality in the highest versus lowest BMI quartile was 0.17 (95% confidence interval=0.05–0.57). CONCLUSION: BMI and WC were negative predictors for all‐cause mortality in older Chinese adults living in long‐term care facilities. Participants with higher WC and BMI had lower all‐cause mortality.     

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus

Aims Mediterranean‐type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean‐type diet improves glycaemic control in diabetes remains unknown. Methods We conducted a cross‐sectional analysis in 901 outpatients with Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA_1c), measured centrally, self‐measured pre‐ and postprandial glucose levels and consumption of a Mediterranean‐type diet. Adherence to a Mediterranean‐type diet was assessed by a 9‐point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA_1c and post‐meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis, mean HbA_1c and 2‐h post‐meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean‐type diet than those with low adherence [difference: HbA_1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2‐h glucose 2.2 mmol/l, 95% CI 0.8–2.9 mmol/l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean‐type diet is associated with lower HbA_1c and postprandial glucose levels.     

Metabolic effects of bariatric surgery in type 2 diabetic patients with body mass index < 35 kg/m2

Aim: The aim of this meta‐analysis is to assess the metabolic effects of bariatric surgery in type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) < 35 kg/m². Methods: We performed an electronic literature search of published articles to identify relevant evidence since inception to June 2011. Primary outcome measures were metabolic improvement and resolution diabetes after bariatric surgery. The weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1) was applied for meta‐analysis. Results: Thirteen trials involving 357 patients were included in the meta‐analysis. The follow‐up interval ranged from 6 months to 18 years. According to WMD calculation, bariatric surgery led to 5.18 kg/m² of BMI lowering (95% CI, 3.79–6.57, p < 0.00001), 4.8 mmol/l of fasting plasma glucose (FPG) decrement (95% CI, 3.88–5.71 mmol/l, p < 0.00001), 2.59% of HbA1c decreasing (95% CI, 2.12–3.07%, p < 0.00001), 56.67 mg/dl of triglyceride decrement (95% CI 11.53–101.82, p = 0.01) and 48.38 mg/dl of total cholesterol reduction (95% CI 21.08–75.68, p = 0.0005). Moreover, the procedures produced an increased high‐density lipoprotein cholesterol by 5.37 mg/dl (95% CI ?11.37–0.63, p = 0.08). However, this effect was not statistically significant. Overall, 80.0% of the patients achieved adequate glycaemic control (HbA1c < 7%) without antidiabetic medication. The surgeries produced a low incidence of major complications (3.2%) with no mortality. Conclusions: Bariatric surgery is effectual and safe in the treatment of non‐severely obese (BMI < 35 kg/m²) T2DM patients. Moreover, the metabolic benefits acquired from the procedures can be long sustained after the surgery.     

The triglyceride-glucose index,a predictor of type 2 diabetes development: A retrospective cohort study

AimsThe triglycerides-glucose (TyG) index, the product of fasting plasma glucose (FPG) and triglycerides (TG) is a novel index. Many previous studies have reported that the TyG index might be a strong predictor of incident type 2 diabetes. We determined whether the TyG index could be a useful predictor for diabetes diagnosis and compared it to the FPG and TG as predictors of type 2 diabetes.MethodsA total of 617 subjects without baseline diabetes were examined and followed up for a median period of 9.2 years. We performed a mixed effect cox regression analysis to evaluate the risk of developing diabetes across the quartiles of the TyG index, calculated as ln[triglyceride (mg/dl) × FPG (mg/dl)/2], and plotted a receiver operating characteristic (ROC) curve to assess discrimination among TyG, FPG and TG.ResultsDuring 4,871.56 person-years of follow-up, there were 163 incident cases of diabetes. The risk of diabetes increased across the quartiles of the TyG index. Those in the highest quartile of TyG had a higher risk of developing diabetes (adjusted HR 3.38 95% CI 2.38–4.8, ptrend < 0.001) than those in the lowest quartile. The area under the curve (AUC) of the ROC plots were 0.79 (95% CI 0.74–0.83) for FPG, 0.64 (95% CI 0.60–0.69) for TyG and 0.59 (95% CI 0.54–0.64) for TG.ConclusionThe TyG index was significantly associated with risk of incident diabetes and could be a valuable biomarker of developing diabetes. However, FPG appeared to be a more robust predictor of diabetes.     

Identification of risk factors affecting impaired glucose metabolism among the adult population of district Srinagar

BackgroundThe World has seen an emerging trend of diabetes among adolescents and moderately aged people over the last decade. The aim of the study was to identify the risk factors associated with impaired glucose metabolism and the prevalence of impaired glucose metabolism among the adult population of district Srinagar.MethodsMulti-stage cluster random sampling design was used and from each household, participants were selected using a Kish grid method. Socio-demographic and clinical data were collected. The participants were then subjected to fasting venous blood glucose estimation.ResultsAge, waist circumference, hip circumference, weight, and body mass index were all statistically significant between normoglycemic participants and those with impaired glucose metabolism (p < 0.018). On logistic regression, subjects who had a higher BMI were more likely to develop Impaired glucose metabolism (OR = 3.52, OR 95% CI = 1.25–9.87); Moreover, consumption of carbonated drinks, (3–6 times/week OR = 4.40, OR 95% CI = 2.06–9.40; >6 times/week OR = 11.04, OR 95% CI = 0.86–140.66) was found to be a potential risk factor. Participants with a family history of diabetes were more susceptible to develop impaired glucose metabolism (OR = 6.41, OR 95% CI = 3.22–12.78). The risk effect of these factors was even stronger before adjusting for age, sex, family history of diabetes, and BMI in participants.ConclusionRisk factors for impaired glucose metabolism include increasing age, obesity, and higher consumption of carbonated drinks, hypertension, smoking behavior, high-calorie diet intake and positive family history of diabetes.     

Body mass index and risk of all‐cause and cardiovascular mortality in hospitalized elderly patients with diabetes mellitus

Aims Obesity is linked to increased morbidity and mortality risk in both the general population and in patients with diabetes mellitus; however, recent reports suggest that, in hospitalized elderly individuals, the association between body mass index (BMI) and mortality may be inverse. The present study sought to investigate the association between BMI and survival in hospitalized elderly individuals with diabetes mellitus. Methods The medical records of 470 patients (226 males, mean age of 81.5 ± 7.0 years) admitted to an acute geriatric ward between 1999 and 2000 were reviewed. Of the 140 patients with diabetes mellitus, 122 had more than 6 months of follow‐up and were included in this analysis. Patients were followed up until 31 August 2004. Mortality data were extracted from death certificates. Results During a mean follow‐up of 3.7 ± 1.6 years, 69 (56.6%) subjects died, 31 (25.4%) from cardiovascular causes. Those who died from any cause had lower baseline BMI than those who survived (24.0 ± 4.0 vs. 27.1 ± 4.3 kg/m²; P < 0.0001). Similarly, those who died of cardiovascular causes had lower baseline BMI than those who did not (23.7 ± 3.6 vs. 25.9 ± 4.5, P = 0.01). BMI was inversely associated with all‐cause [relative risk (RR) 0.89, 95% confidence interval (CI) 0.83–0.96, P = 0.002] and cardiovascular death (RR 0.83, 95% CI 0.74–0.93, P = 0.002) even after controlling for age, sex, smoking, dyslipidaemia and reason for hospital admission. Conclusions In very elderly subjects with diabetes mellitus, increased BMI was associated with reduced mortality risk.     

Hyperinsulinaemia in youth is a predictor of Type 2 (non-insulin-dependent) diabetes mellitus

Summary This study aimed to compare plasma insulin concentrations across the age-range from childhood to old age in the populations of Nauru and Tuvalu, and to assess their relationship to the incidence of impaired glucose tolerance and diabetes in young Nauruans. The studies, performed in 1975 and 1976, found that Nauru had a higher prevalence of Type 2 (non-insulin-dependent) diabetes mellitus than Tuvalu. Both studies included subjects of 8–29 years of age (n=320 in Nauru, n=318 in Tuvalu) and on these subjects glucose tolerance status, body mass index and fasting and 2-h (post 75 g glucose load) plasma insulin concentrations were determined. In Nauru, follow-up surveys in 1982 and 1987 included many of the subjects first seen in 1975/1976, allowing the incidence and natural history of glucose intolerance to be studied. Within the group of subjects with normal glucose tolerance, there was no effect of age on plasma insulin distributions in either population. However, in both populations, 8–19 year old subjects with normal glucose tolerance had higher body mass index-adjusted geometric mean fasting and 2-h insulin concentrations than older age-groups (p < 0.001 for fasting insulin). Body mass index-adjusted geometric mean 2-h plasma insulin was higher in subjects with abnormal glucose tolerance relative to those with normal glucose tolerance in both populations. In Nauruans, 2-h insulin levels at baseline were predictive of impaired glucose tolerance and Type 2 diabetes in 1982, and fasting and 2-h insulin levels predicted development of Type 2 diabetes in 1987. Hyperinsulinaemia in the presence of normal glucose tolerance is evident in young people in Nauru and Tuvalu, as has been demonstrated in other populations known to have high susceptibility to Type 2 diabetes. Even in youth, elevated fasting and 2-h insulin concentration is predictive of subsequent deterioration in glucose tolerance.     

U‐shape association between white blood cell count and the risk of diabetes in young Chinese adults

Background Chronic low‐grade inflammation is related to diabetes risk in population studies. Elevated levels of white blood cells (WBC) were related to the risk of diabetes in cross‐sectional studies in the Chinese population. The objective of the study is to assess the prospective association between WBC and the risk of diabetes in the Chinese population. Methods We examined 7445 manual workers aged 18–59 years free from diabetes at baseline. Fasting glucose concentrations and white cell count were measured at annual health examinations from 1997 to 2007. Anthropometric measurements were taken by health workers. In the present study, each participant had at least two measurements of fasting blood glucose. Results During a mean of 4.94 years follow‐up, 178 participants developed diabetes. After controlling for known risk factors for diabetes (age, gender, smoking, drinking, parental history of diabetes, body mass index, systolic blood pressure, hepatitis B surface antigen and liver function), a U‐shaped association between WBC count and diabetes was found. The hazard ratios (HR) of diabetes across quartiles of WBC count were 1.87 (95% CI 1.15–3.05), 1.00, 1.46 (0.88–2.42) and 2.04 (1.28–3.25). The association was stronger among non‐smokers: compared with the second quartile, the HR of diabetes for the first and fourth quartiles of WBC were 3.00 (1.28–7.03) and 3.16 (1.33–7.53). Adjusting for hepatitis B virus infection and liver function did not change the association. Conclusion Both low and high levels of WBC count were associated with an increased risk of diabetes in young workers.     

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes

Aims To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. Methods One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20–71 years underwent cross‐sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x‐ray absorptiometry. BMD data were available for 102 age‐ and gender‐matched population‐based control subjects. Results After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T‐ and Z‐scores at the hip, femoral neck and spine were lower compared with age‐matched control subjects (P ≤ 0.048). Female Type 1 patients and control subjects had similar BMDs and T‐ and Z‐scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. Conclusions Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age‐matched control subjects. Impaired bone formation may occur in Type 1 diabetes.     

Metabolic characteristics of autoimmune diabetes mellitus in adults

Summary It is still a matter of debate whether patients who develop islet-cell antibody positive autoimmune diabetes during adulthood represent slowly evolving Type 1 (insulindependent) diabetes mellitus or a separate subgroup of Type 2 (non-insulin-dependent) diabetes. To address this question, we measured C-peptide response to a test meal, and energy metabolism in the basal state and during a euglycaemic, hyperinsulinaemic clamp in (1) 29 patients with Type 2 diabetes; (2) 10 patients with autoimmune diabetes developing after the age of 40 years; (3) 11 patients with Type 1 diabetes and (4) 15 non-diabetic control subjects. While C-peptide response to a test meal was lacking in Type 1 diabetes and nearly normal in Type 2 diabetes, the C-peptide response in autoimmune diabetes was markedly reduced. Patients with Type 2 diabetes, autoimmune diabetes and Type 1 diabetes showed a 47%, 45% and 42%, respectively, reduction in the rate of non-oxidative glucose metabolism compared with control subjects (p<0.05-0.01). Similarly, patients with Type 2 diabetes (+52%), autoimmune diabetes (+27%) and Type 1 diabetes (+33%) presented with an enhanced basal rate of hepatic glucose production, which was less suppressed by insulin compared with healthy control subjects (p<0.01). However, patients with autoimmune diabetes derived more energy from oxidation of glucose and proteins and less energy from oxidation of lipids than patients with either Type 1 or Type 2 diabetes (p<0.05-0.01). In conclusion, patients who develop autoimmune diabetes during adulthood share the defects in hepatic glucose production and in non-oxidative glucose metabolism with both Type 1 and Type 2 diabetes. Oxidative energy metabolism in autoimmune diabetes, however, differs from that observed in Type 1 and Type 2 diabetes. Given the metabolic characteristics of these patients, it seems justified to consider autoimmune diabetes in adults as a subgroup of diabetes developing in adult age.     

Pharmacokinetic and pharmacodynamic profile of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial

Aims

To assess the pharmacokinetic and pharmacodynamic profile of a single dose of empagliflozin in young people with Type 2 diabetes to identify the appropriate doses for further paediatric development.

Methods

We conducted a single‐dose, open‐label, randomized, parallel‐group study with empagliflozin 5 mg, 10 mg and 25 mg in young people with Type 2 diabetes aged 10–17 years.

Results

Of 39 participants screened, 27 were randomized and completed the study; their mean (± sd ) age was 14.1±2.0 years and body weight was 96.7±23.5 kg. Compared with similar studies in adults with Type 2 diabetes, the maximum observed plasma concentrations were slightly lower with the 10‐mg and 25‐mg doses, and the area under the plasma concentration–time curve was slightly lower with the 10‐mg but slightly higher with the 25‐mg dose. The adjusted mean increases in urinary glucose excretion were 53 g/24 h (95% CI 32,74), 73 g/24 h (95% CI 52,94) and 87 g/24 h (95% CI 68,107), and the adjusted mean decreases in fasting plasma glucose were 0.9 mmol/l (95% CI –1.6,–0.1), 0.9 mmol/l (95% CI –1.7,–0.2) and 1.1 mmol/l (95% CI –1.8,–0.5) for the 5‐ 10‐ and 25‐mg doses, respectively. There were no serious adverse events and one investigator‐reported drug‐related event (dehydration).

Conclusions

After a single oral dose of empagliflozin, adults and young people with Type 2 diabetes had similar exposure–response relationships after adjusting for significant covariates. These data support testing 10‐mg and/or 25‐mg doses of empagliflozin in an upcoming paediatric phase III Type 2 diabetes trial. (ClinicalTrials.gov registration no.: NCT02121483).     

The impact of Type 2 diabetes and microalbuminuria on future cardiovascular events in patients with clinically manifest vascular disease from the Second Manifestations of ARTerial disease (SMART) study

Aims Type 2 diabetes mellitus and microalbuminuria are important risk factors for cardiovascular disease (CVD). Whether these two complications are important and independent risk factors for future CVD events in a high‐risk population with clinically manifest vascular disease is unknown. The objectives of this study were to examine the impact of Type 2 diabetes and microalbuminuria on future CVD events. Methods Patients with clinically manifest vascular disease (coronary, cerebral and peripheral vascular disease) from the Second Manifestation of Arterial disease study were followed up for 4 years. Data obtained from 1996–2006 were analysed. At baseline, there were 804 patients with Type 2 diabetes mellitus (mean age 60 years) and 2983 patients without. Incident CVD (n = 458) was defined as hospital‐verified myocardial infarction, stroke, vascular death and the composite of these vascular events. Results Both Type 2 diabetes [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.16, 1.75] and microalbuminuria (HR 1.86, 95% CI 1.49, 2.33) increased the risk of new cardiovascular events in univariate analyses. From multivariable models, presence of diabetes remained significantly and independently related to incident CVD (HR 1.42, 95% CI 1.11, 1.80). Presence of microalbuminuria also remained significantly independently related to incident CVD (HR 1.38, 95% CI 1.07, 1.77). In diabetes‐stratified analyses, the effect of microalbuminuria on CVD risk was observed only in patients with diabetes. In microalbuminuria‐stratified analyses, the significant and independent effect of diabetes on CVD risk was shown only in the non‐microalbuminuric group. Conclusions In this high‐risk population, both microalbuminuria and Type 2 diabetes are important and independent risk factors for future CVD.     

Determinants of adiponectin levels in young people with Type 1 diabetes

Aims To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non‐diabetic controls, and explore potential determinants for this difference. Methods Data are from the SEARCH for Diabetes in Youth Case‐Control Study. A total of 440 youth with Type 1 diabetes and 191 non‐diabetic healthy controls age 10–22 years of non‐Hispanic White (NHW), African‐American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA_1c). Results Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 µg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA_1c in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity. Conclusions Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.     

Diabetes in the Caribbean: results of a population survey from Spanish Town, Jamaica.

AIMS: To characterize the prevalence of diabetes and associated risk attributes in the Jamaican population. METHODS: A random population sample was recruited by door-to-door canvassing (n = 1303). A final participation of 60% was achieved. Oral glucose tolerance testing was conducted after an overnight fast and standard anthropometric and demographic data were collected. RESULTS: The prevalence of Type 2 diabetes mellitus was 9.8% (95% confidence interval (CI) 7.2-12.4) among men and 15.7% (95% CI 13.1-18.3) among women with an overall prevalence of 13.4% (95% CI 11.5-15.2). Impaired glucose tolerance was found among 12.3% of men and 14.7% of women. The sex patterns were consistent with a fourfold excess of obesity in women compared to men. The odds ratios for diabetes, fourth vs. first quartiles were 5.42 (95% CI 2.02-16.88) in men and 3.32 (95% CI 1.73-6.63) in women for body mass index (BMI) and 17.39 (95% CI 3.86-78.27) in men and 5.48 (95% CI 2.84-11.00) in women for WHR in a logistic model controlling for age. The population attributes risk percentage, for diabetes, of being overweight and having waist-to-hip ratio (WHR) greater than the median (0.80) were 66% and 80%, respectively. The contribution of central obesity, as characterized by WHR, was also significant in sex-specific multivariate models that included age and BMI. Prevalent hypertension and family history of diabetes were likewise associated with increased odds of having the disease. CONCLUSIONS: The prevalence of diabetes in Jamaica now exceeds that observed among European-origin populations and reflects the emerging epidemic of obesity. The excess risk for this population could not be attributed entirely to relative weight. The pronounced sexual dimorphism in diabetes prevalence most likely reflects the substantial excess of obesity among women compared to men. Like many other island nations, Caribbean societies now appear to be at substantial risk of diabetes.     

Congenital anomalies in the offspring of women with type 1, type 2 and gestational diabetes.

AIM: To determine the frequency of major congenital anomalies in the offspring of women with gestational diabetes (GDM), classified according to their postpartum glucose tolerance status. METHODS: A prospective study of pregnancies in women with Type 1 diabetes (n = 221), Type 2 diabetes (n = 317) and GDM (n = 1822) between 1985 and 2000 (15 years). Congenital anomalies were detected by antenatal ultrasound or postnatal examination. RESULTS: The frequency of major congenital anomalies in the offspring was 5.9% (95% confidence interval (CI) 3.2-9.8) for women with Type 1 diabetes; 4.4% (95% CI 2.4-7.3) for women with Type 2 diabetes; and 1.4% (95% CI 0.9-2.0) for women with GDM. Two hundred and thirty-seven women with GDM (13%) had diabetes diagnosed on early (6-week) postpartum glucose tolerance testing. The frequency of major congenital anomalies in their offspring was 4.6% (95% CI 2.3-8.2), compared with 0.9% (95% CI 0.5-1.5) for the remainder of the GDM group (P < 0.0001). CONCLUSIONS: GDM is not a homogeneous group with regard to the risk of major congenital anomalies. In those with diabetes on early postpartum testing, who are likely to have had unrecognized Type 2 diabetes antedating their pregnancy, the rate of major congenital anomalies is the same as for women with established Type 1 or Type 2 diabetes. In the remainder of the GDM group, the rate does not differ from the non-diabetic background rate.