Diabetes,plasma insulin,and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)

BACKGROUND: Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. OBJECTIVES: To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. METHODS: Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04). CONCLUSION: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.     

Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.

BACKGROUND: The contributions of fasting and 2-hour postchallenge glucose level to cardiovascular events remain ill-defined, especially for nondiabetic adults. This study examined the relative predictive power of fasting and 2-hour glucose level on cardiovascular event risk. METHODS: A total of 4014 community-dwelling adults 65 years or older who participated in the baseline visit of the Cardiovascular Health Study and who were without treated diabetes or previous myocardial infarction or stroke were eligible for analyses. Participants with treated diabetes at baseline were excluded. Incident myocardial infarction or stroke, or coronary death, was the outcome of interest. Age-, sex-, and race-adjusted proportional hazards regression models described individual and joint associations between baseline measures of fasting and 2-hour postchallenge glucose level and event risk. RESULTS: There were 764 incident cardiovascular events during 8.5 years of follow-up. Fasting glucose level of 115 mg/dL (6.4 mmol/L) or more was associated with an increased cardiovascular risk (hazard ratio [HR], 1.66 [95% confidence interval (CI), 1.39-1.98]) in adjusted analyses compared with fasting glucose level less than 115 mg/dL. Two-hour glucose level was associated with a linear risk (HR, 1.02 [95% CI, 1.00-1.04] per 10 mg/dL [0.6 mmol/L]) that included an additional increase in risk for 2-hour glucose level of 154 mg/dL (8.5 mmol/L) or more (HR, 1.29 [95% CI, 1.04-1.59]) in adjusted analyses. In joint fasting and 2-hour glucose models, only 2-hour glucose level remained predictive of event risk. CONCLUSIONS: Two-hour glucose level was better than fasting glucose level alone at identifying older adults at increased risk of major incident cardiovascular events.     

Association of diabetes, serum insulin, and C-peptide with gallbladder disease

An inconsistent association has been found between gallbladder disease and diabetes mellitus. We hypothesized that insulin resistance rather than diabetes status may be a primary factor involved in gallstone formation. A total of 5,653 adult participants in the third United States National Health and Nutrition Examination Survey without known diabetes underwent gallbladder ultrasonography and phlebotomy after an overnight fast for measurement of serum insulin, C-peptide, and glucose. Gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. Subjects were characterized as having normal fasting glucose (<110 mg/dL), impaired fasting glucose (110 to <126 mg/dL), or undiagnosed diabetes (>/=126 mg/dL). After controlling for other known gallbladder disease risk factors, among women, undiagnosed diabetes was associated with increased risk of gallbladder disease (prevalence ratio [PR] = 1.91, 95% confidence interval [CI] = 1.29-2. 83); whereas impaired fasting glucose was unassociated. Gallbladder disease risk in women increased with levels of fasting insulin (PR = 1.63, 95% CI = 1.11-2.40) and C-peptide (PR = 2.07, 95% CI = 1.32-3. 25) comparing highest to lowest quintiles. However, the association of gallbladder disease with undiagnosed diabetes was not diminished when the model included fasting insulin (PR = 1.85, 95% CI = 1.24-2. 77). In men, there was a statistically nonsignificant association with undiagnosed diabetes (PR = 2.11, 95% CI = 0.76-5.85), but no association of gallbladder disease with insulin or C-peptide. Among women higher fasting serum insulin levels increased the risk of gallbladder disease, but did not account for the increased risk in persons with diabetes.     

Glycemic Status and Incident Heart Failure in Elderly Without History of Diabetes Mellitus: The Health, Aging, and Body Composition Study

BackgroundIt is unclear whether measures of glycemic status beyond fasting glucose (FG) levels improve incident heart failure (HF) prediction in patients without history of diabetes mellitus (DM).Methods and ResultsThe association of measures of glycemic status at baseline (including FG, oral glucose tolerance testing [OGTT], fasting insulin, hemoglobin A_1c [HbA_1c] levels, and homeostasis model assessment of insulin resistance [HOMA-IR] and insulin secretion [HOMA-B]) with incident HF, defined as hospitalization for new-onset HF, was evaluated in 2386 elderly participants without history of DM enrolled in the Health, Aging, and Body Composition Study (median age, 73 years; 47.6% men; 62.5% white, 37.5% black) using Cox models. After a median follow-up of 7.2 years, 185 (7.8%) participants developed HF. Incident HF rate was 10.7 cases per 1000 person-years with FG <100 mg/dL, 13.1 with FG 100–125 mg/dL, and 26.6 with FG ≥126 mg/dL (P = .002; P = .003 for trend). In adjusted models (for body mass index, age, history of coronary artery disease and smoking, left ventricular hypertrophy, systolic blood pressure and heart rate [HR], and creatinine and albumin levels), FG was the strongest predictor of incident HF (adjusted HR per 10 mg/dL, 1.10; 95% CI, 1.02–1.18; P = .009); the addition of OGTT, fasting insulin, HbA_1c, HOMA-IR, or HOMA-B did not improve HF prediction. Results were similar across race and gender. When only HF with left ventricular ejection fraction (LVEF) ≤40% was considered (n = 69), FG showed a strong association in adjusted models (HR per 10 mg/dL, 1.15; 95% CI, 1.03–1.29; P = .01). In comparison, when only HF with LVEF >40%, was considered (n = 71), the association was weaker (HR per 10 mg/dL, 1.05; 95% CI; 0.94–1.18; P = .41).ConclusionsFasting glucose is a strong predictor of HF risk in elderly without history of DM. Other glycemic measures provide no incremental prediction information.     

Normal fasting plasma glucose and risk of type 2 diabetes diagnosis

Purpose

The study compares the risk of incident diabetes associated with fasting plasma glucose levels in the normal range, controlling for other risk factors.

Methods

We identified 46,578 members of Kaiser Permanente Northwest who had fasting plasma glucose levels less than 100 mg/dL between January 1, 1997, and December 31, 2000, and who did not previously have diabetes or impaired fasting glucose. After assigning subjects to 1 of 4 categories (<85, 85-89, 90-94, or 95-99 mg/dL), we followed them until they developed diabetes, died, or left the health plan, or until April 30, 2007. We used Cox regression analysis to estimate the risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension.

Results

Subjects developed diabetes at a rate of less than 1% per year during a mean follow-up of 81.0 months. Each milligram per deciliter of fasting plasma glucose increased diabetes risk by 6% (hazard ratio [HR] 1.06, 95% confidence interval [CI], 1.05-1.07, P < .0001) after controlling for other risk factors. Compared with those with fasting plasma glucose levels less than 85 mg/dL, subjects with glucose levels of 95 to 99 mg/dL were 2.33 times more likely to develop diabetes (HR 2.33; 95% CI, 1.95-2.79; P < .0001). Subjects in the 90 to 94 mg/dL group were 49% more likely to progress to diabetes (HR 1.49; 95% CI, 1.23-1.79; P <.0001). All other risk factors except sex were significantly associated with a diabetes diagnosis.

Conclusions

The strong independent association between the level of normal fasting plasma glucose and the incidence of diabetes after controlling for other risk factors suggests that diabetes risk increases as fasting plasma glucose levels increase, even within the currently accepted normal range.     

Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history

Fasting plasma glucose level was linearly associated with colorectal cancer (CRC) risk. However, the dose–response relationship between fasting blood glucose (FBG) and CRC risk was still uncertain.A total of 11,632 patients without self-reported diabetes mellitus and colorectal polyps’ history were identified in the Korean Multicenter Cancer Cohort (1993–2005). The nonlinear relationship was estimated through a restricted cubic spline regression, and a two-piece-wise Cox proportional hazards model was further performed to calculate the threshold effect. Multiple imputation was used to control the bias from missing data.Overall, 1.1% (n = 132) of participants were diagnosed with CRC in the follow-up duration. With a median follow-up duration of 12.0 years, participants with FBG ≥126 mg/dL were associated with higher CRC risk (adjusted hazard ratio [HR], 1.67; 95% confidence interval [CI]: 1.01, 2.76). Landmark analyses limited to long-term survivors demonstrated increased CRC risk with FBG ≥ 126 mg/dL in all subsets (≥3years: HR,1.93 (95% CI: 1.13–3.29); ≥5years: HR, 2.04 (95% CI: 1.–3.63); ≥10years: HR, 2.50 (95% CI: 1.19–5.25)). With FBG smoothly increasing before, the latter increased dramatically after the turning point (P for nonlinearity = 0.283). When FBG was increasing per mmol/L, HR was 1.07(95% CI: 0.90, 1.29) for FBG < 126 mg/dL and 1.27 (95% CI: 1.06, 1.53) for FBG ≥ 126 mg/dL. Besides, HR was 1.09 (95% CI: 1.02, 1.16) for the CRC risk.In the population without self-reported diabetes mellitus and colorectal polyps’ history. FBG was linearly associated with CRC risk, especially for FBG over 126 mg/dL.     

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.     

Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundAlthough diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A_1C [HbA_1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF.Methods and ResultsWe included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000–2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57–2.68) and HFrEF (HR 2.02, 95% CI 1.38–2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA_1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21–3.17; HR for HbA_1C 2.00, 95% CI 1.20–3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18–2.88; HR for HbA_1C 1.99, 95% CI 1.28–3.09) compared with reference values. Prediabetic range HbA_1C (5.7%–6.4%) or FPG (100%–125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF.ConclusionsAmong community-dwelling individuals, HbA_1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.Lay AbstractHeart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A_1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A_1C were similarly associated with higher risks of both types of HF.     

Leptin and incident type 2 diabetes: risk or protection?

Aims/hypothesis The aim of this study was to investigate the association of leptin levels with incident diabetes in middle-aged adults, taking into account factors purportedly related to leptin resistance.Subjects and methods We conducted a case–cohort study (570 incident diabetes cases and 530 non-cases) representing the 9-year experience of 10,275 participants of the Atherosclerosis Risk in Communities Study. Plasma leptin was measured by direct sandwich ELISA.Results In proportional hazards models adjusting for age, study centre, ethnicity and sex, high leptin levels (defined by sex-specific cut-off points) predicted an increased risk of diabetes, with a hazard ratio (HR) comparing the upper with the lower quartile of 3.9 (95% CI 2.6–5.6). However, after further adjusting additionally for obesity indices, fasting insulin, inflammation score, hypertension, triglycerides and adiponectin, high leptin predicted a lower diabetes risk (HR=0.40, 95% CI 0.23–0.67). Additional inclusion of fasting glucose attenuated this protective association (HR=0.59, 95% CI 0.32–1.08, p<0.03 for linear trend across quartiles). In similar models, protective associations were generally seen across subgroups of sex, race, nutritional status and smoking, though not among those with lower inflammation scores or impaired fasting glucose (interaction p=0.03 for both).Conclusions/interpretation High leptin levels, probably reflecting leptin resistance, predict an increased risk of diabetes. Adjusting for factors purportedly related to leptin resistance unveils a protective association, independent of adiponectin and consistent with some of leptin’s described protective effects against diabetes.     

Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.     

Bartter综合征中的高胰岛素血症

目的 探讨Bartter综合征与胰岛素抵抗、葡萄糖代谢异常之间的关系.方法 选择北京协和医院2003年9月至2008年5月期间诊治的23例Bartter综合征患者[年龄(27±9)岁,空腹血钾(2.8±0.5)mmol/L],20例醛固酮瘤(APA)患者[年龄(45±11)岁,空腹血钾(3.0±0.4)mmol/L]及20例特发性醛固酮增多症(IHA)患者[年龄(51±11)岁,空腹血钾(3.4±0.2)mmol/L]作为研究对象.所有受试对象均行卧立位醛固酮试验和3 h口服葡萄糖耐量试验(3hOGTT),以稳态模型(HOMA)公式计算胰岛素抵抗指数(HOMA-IR)和胰岛素分泌指数(HOMA-IS).结果 Bartter综合征组与IHA组的胰岛素曲线下面积差异无统计学意义[(229.0±162.4)mIU·L-1·h比(227.7±158.6)mIU·L-1·h],明显高于APA组(121.2±81.1)mIU·L-1·h.但Bartter综合征组与APA组的HOMA-IR值差异无统计学意义(1.96±1.14比1.41±0.91),APA组HOMA-IR值显著低于IHA组(2.40±1.59).3组患者HOMA-IS值差异无统计学意义,但APA组[81.7(55.1,181.2)]有低于Bartter组[151.7(102.4,265.5)]和IHA组[131.0(76.5,184.7)]的趋势.3组患者胰岛素分泌高峰均延迟至2 h.结论 Bartter综合征患者存在高胰岛素血症.

Abstract：

Objective To analys hyperinsulinemia in Bartter syndrome. Methods Twenty-three cases of Bartter syndrome [age (27 ±9) years;fasting serum potassium(2. 8 ±0. 5)mmol/L], 20 patients of aldosterone-producing adenoma [APA, age (45 ± 11 ) years, fasting serum potassium ( 3.0 ± 0. 4 ) mmol/L], 20 patients of idiopathic hyperaldosteronism [IHA, age (51 ± 11 ) years, fasting serum potassium (3.4 ±0. 2)mmol/L] were diagnosed in Peking Union Medical College Hospital from September 2003 to May 2008. All patients underwent 3-hours oral glucose tolerance test(3hOGTT), postural stimulation test and calculated HOMA-insulin resistance ( HOMA-IR ) and HOMA-insulin sensitivity ( HOMA-IS ) by Homeostasis model.Results The insulin area under curve-(229.0±162.4)mIU·L-1·h] was singnificantly higher than APA group [(227.7±158.6)mIU·-1·h].But HOMA-IR in Bartter group were similar to APA group( 1.96 ± 1.14 vs 1.41 ± 0. 91 ), and HOMA-IR in APA group was lower than IHA group ( 1.96 ± 1.14 vs 2.40 ± 1.60, P ＜ 0. 05 ). There was no deference in HOMA-IS among three groups,but APA group had lower level. In all three groups, the peak of insulin secretion was delayed. Conclusion Bartter syndrome patients commonly present with hyperinsulinemia.     

Association between insulin, insulin resistance, and gallstone disease in Korean general population]

BACKGROUND/AIMS: Diabetes is one of the risk factors of gallstone diseases. Many studies found a positive association between insulin and gallstones in individuals with diabetes. However, this association is unclear in non-diabetes. So we conducted a case-control study for the evaluation of the association between gallstone diseases and fasting serum insulin level, insulin resistance in non-diabetic Korean general population. METHODS: This study was a prospective case-control study on 118 Korean subjects which included clinical examination, abdominal ultrasound, and blood chemistries. Serum fasting insulin level were determined by radioimmunoassay and concentrations of cholesterol, glucose, and triglycerides by standard enzymatic colorimetric methods. Insulin resistance was determined by the homeostasis model assessment (HOMA-IR). Body mass index (BMI), percentage of body fat, and waist hip ratio were also measured. RESULTS: We studied 118 subjects with no clinical evidence of diabetes mellitus and serum glucose <126 mg/dL. Compared with controls (n=89), cases (n=29) had higher levels of serum insulin, glucose, triglyceride levels, and BMI. In t-test and chi-square test for variables, the association between gallstone disease and serum insulin, HOMA-IR index, and BMI were statistically significant (p<0.05). In multiple logistic regression analysis, gallstone disease risk increased with the level of serum insulin (p=0.024, odds ratio=1.376) and HOMA-IR index (p=0.013, odds ratio=2.006). CONCLUSIONS: We suggest that hyperinsulinemia and insulin resistance could be associated with gallstone formation in individuals without clinical diagnosis of diabetes mellitus and with normal serum glucose level.     

Impaired glucose tolerance is a more advanced stage of alteration in the glucose metabolism than impaired fasting glucose

BACKGROUND: Recent reports have shown a lack of agreement between the impaired glucose tolerance (IGT) and the impaired fasting glucose (IFG) categories, suggesting that correspond to different impaired glucose metabolism stages. OBJECTIVE: To determine the differences of serum insulin levels between subjects with IFG and IGT diagnoses. METHODS: Cross-sectional study of 52 subjects with IFG and 48 with IGT diagnosis, and a euglycemic group of 140 subjects. Serum glucose and insulin were measured in both fasting and 2-h 75-g oral post-load glucose (2-h PG). RESULTS: Subjects with IFG showed the highest fasting and 2-h PG serum insulin levels, whereas subject with IGT the lowest. Serum insulin values showed no significative changes between the fasting and 2-h PG conditions in the subjects with IGT, whereas the subjects with IFG showed significative hyperinsulinemia. The serum glucose 2-h PG showed an increase of 0.2 mmol/l (CI(95%) 0.07-0.33), 0.5 mmol/l (CI(95%) 0.41-0.58) and 3.6 mmol/l (CI(95%) 3.39-3.81) with respect to basal values, whereas the increase of serum insulin 2-h PG was of 54 pmol/l (CI(95%) 53.71-55.29), 918 pmol/l (CI(95%) 917.49-918.51) and 0.5 pmol/l (CI(95%) 0.15-0.84) for the euglycemic, IFG and IGT subjects, respectively. CONCLUSIONS: This study demonstrates that subjects with IFG show hyperinsulinemia whereas those with IGT have low insulin secretion in response to oral load glucose, suggesting that IFG and IGT correspond to different stages of impaired glucose metabolism.     

Insulin resistance in Brazilian adolescent girls: association with overweight and metabolic disorders

We assessed the association between insulin resistance, overweight and metabolic disorders in a probabilistic sample of 388, 12-19-year-old girls from public schools in Niterói, Rio de Janeiro State, Brazil. Insulin resistance was determined using Homeostatic Model Assessment-Insulin Resistance (HOMA-IR). Overweight and obesity were defined by the sex- and age-specific body mass index cut-offs recommended by the International Obesity Task Force. Metabolic syndrome (MS) was identified by the presence of at least three of the following factors: fasting glucose >or=100mg/dL, triglycerides >130 mg/dL, LDL-C >or=110 mg/dL, HDL-C <35 mg/dL and overweight. The combined prevalence of obesity (2.9%) and overweight was 14.2%. The average HOMA-IR level was 2.24 (95% confidence interval=1.40-3.10) in the overweight group and 1.91 (95% CI=1.32-2.50) in the non-overweight one, and MS prevalence was 20 times higher in the first group (21.4 and 0.1%). MS prevalence in the overweight group was 6.3 times higher in adolescents above the 66th percentile of HOMA-IR (55.9%) than those under the 33rd percentile (8.9%). Brazilian overweight girls with higher insulin resistance had high risk of developing MS. Therefore, prevention should occur at an early age to impair the evolution of this process.     

Fracture risk in diabetic elderly men: the MrOS study

Aims/hypothesis

Diabetes mellitus is associated with increased fracture risk in women but few studies are available in men. To evaluate the relationship between diabetes and prospective non-vertebral fractures in elderly men, we used data from the Osteoporotic Fractures in Men (MrOS) study.

Methods

The MrOS enrolled 5,994 men (aged ≥65 years). Diabetes (ascertained by self-report, the use of medication for diabetes or an elevated fasting glucose level) was reported in 881 individuals, 80 of whom were using insulin. Hip and spine bone mineral density (BMD) was measured using dual x-ray absorptiometry (DXA). After recruitment, the men were followed for incident non-vertebral fractures using a triannual (3 yearly) questionnaire for an average of 9.1 (SD 2.7) years. The Cox proportional hazards model was used to assess the incident risk of fractures.

Results

In models adjusted for age, race, clinic site and total hip BMD, the risk of non-vertebral fracture was higher in men with diabetes compared with normoglycaemic men (HR 1.30, 95% CI 1.09, 1.54) and was elevated in men using insulin (HR 2.46, 95% CI 1.69, 3.59). Men with impaired fasting glucose did not have a higher risk of fracture compared with normoglycaemic men (HR 1.04, 95% CI 0.89, 1.21). After multivariable adjustment, the risk of non-vertebral fracture remained higher only among men with diabetes who were using insulin (HR 1.74, 95% CI 1.13, 2.69).

Conclusions/interpretation

Men with diabetes who are using insulin have an increased risk of non-vertebral fracture for a given age and BMD.     

Insulin resistance and fasting hyperinsulinemia are risk factors for new cardiovascular events in patients with prior coronary artery disease and normal glucose tolerance.

BACKGROUND: Insulin resistance and hyperinsulinemia are important risk factors for coronary artery disease (CAD) and cardiovascular event (CVE). However, their independent relationship to new CVE in patients with normal glucose tolerance (NGT) and CAD is not known. METHODS AND RESULTS: Subjects of this 3-year observational study were 102 patients with CAD. Plasma glucose and insulin concentrations were determined at 2 time points (baseline and post oral glucose tolerance test [OGTT]. The fasting plasma glucose <110 mg/dl and post-OGTT <140 mg/dl was diagnosed as NGT (World Health Organization criteria). Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR). Of the 102 patients, 23 had onset of new CVE, including 19 with new CAD. They had significantly higher fasting and post-OGTT insulin levels and HOMA-IR than those without new CVE (P<0.01, 0.031 and <0.01, respectively). Using the univariate Cox proportional hazards model, fasting and post-OGTT insulin values, HOMA-IR and high density lipoprotein (HDL) cholesterol differed significantly between the 2 groups. The multivariate Cox model showed that the effect of fasting plasma insulin and HOMA-IR remained significant and independent of HDL cholesterol. CONCLUSION: Fasting hyperinsulinemia and high insulin resistance increased the risk of new CVE in patients with NGT and CAD.     

Insulin resistance syndrome in a representative sample of children and adolescents from Quebec, Canada

OBJECTIVES: To estimate the prevalence of insulin resistance syndrome (IRS) in a representative sample of youth. To test for the independent contribution of insulin resistance (IR) and adiposity to clustering of metabolic risk factors. To identify the underlying components of IRS. To examine the relationship between adiposity and fasting plasma levels of free fatty acids (FFA). METHODS: In 1999, we conducted a school-based survey of a representative sample of youth aged 9, 13 and 16 y in Quebec, Canada. Age-specific questionnaire data, standardized clinical measurements and a fasting blood sample were available for 2244 subjects. Fasting insulin and HOMA were used as surrogate measures of IR. RESULTS: In all age-sex groups, adiposity indices, blood pressure (BP), plasma glucose and triglycerides (TG) increased significantly with increasing insulin quartiles while HDL cholesterol (HDL-C) decreased. The overall prevalence of IRS defined as hyperinsulinaemia combined with two or more risk factors including overweight, high systolic BP, impaired fasting glucose, high TG and low HDL-C, was 11.5% (95% CI: 10.2-12.9). There were no significant differences in the prevalence of IRS across ages or between sexes. The independent contribution of adiposity to clustering of risk factors was stronger than that of fasting insulin (or HOMA-IR). Factor analysis revealed three factors (BMI/insulin/lipids, BMI/insulin/glucose and diastolic/systolic BP) consistent across ages suggesting that more than one pathophysiologic process underlies IRS. Although elevation of FFA might be in the causal pathway linking obesity to IR, we did not detect any consistent association between measures of fatness and fasting plasma FFA. CONCLUSION: IRS is highly prevalent in youth, even among children as young as age 9 y. Factor analysis identifies three physiologic domains within IRS with a unifying role for markers of IR and adiposity.     

Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes; however, this association has not been examined prospectively. METHODS: We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults (N = 12,128) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up. Fasting serum magnesium level, categorized into 6 levels, and dietary magnesium intake, categorized into quartiles, were measured at the baseline examination. Incident type 2 diabetes was defined by self-report of physician diagnosis, use of diabetic medication, fasting glucose level of at least 7.0 mmol/L (126 mg/dL), or nonfasting glucose level of at least 11.1 mmol/L (200 mg/dL). RESULTS: Among white participants, a graded inverse relationship between serum magnesium levels and incident type 2 diabetes was observed. From the highest to the lowest serum magnesium levels, there was an approximate 2-fold increase in incidence rate (11.1, 12.2, 13.6, 12.8, 15.8, and 22.8 per 1000 person-years; P = .001). This graded association remained significant after simultaneous adjustment for potential confounders, including diuretic use. Compared with individuals with serum magnesium levels of 0.95 mmol/L (1.90 mEq/L) or greater, the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories: 1.13 (95% CI, 0.79-1.61), 1.20 (95% CI, 0.86-1.68), 1.11 (95% CI, 0.80-1.56), 1.24 (95% CI, 0.86-1.78), and 1.76 (95% CI, 1.18-2.61) (for trend, P = .01). In contrast, little or no association was observed in black participants. No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in black or white participants. CONCLUSIONS: Among white participants, low serum magnesium level is a strong, independent predictor of incident type 2 diabetes. That low dietary magnesium intake does not confer risk for type 2 diabetes implies that compartmentalization and renal handling of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes.     

Size and shape of the associations of glucose,HbA<Subscript>1c</Subscript>, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

Aims/hypothesis

Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA_1c, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus.

Methods

The study population included 1349 participants aged 50–75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations.

Results

After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA_1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA_1c with incident diabetes were non-linear, rising more steeply at higher values.

Conclusions/interpretation

FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA_1c, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

     

Prognostic value of glycated hemoglobin in colorectal cancer

AIM To investigate the clinical significance of routinely used glycemic parameters in a cohort of colorectal cancer(CRC) patients.METHODS Pre-treatment fasting blood glucose, insulin, Hb A1 c and homeostasis model of risk assessment(HOMA-IR) were retrospectively evaluated in a case-control study of 224 CRC and 112 control subjects matched for sex, obesity and diabetes frequency and blood lipid profile.Furthermore, the prognostic value of routinely used glycemic parameters towards progression-free(PFS) and overall survival(OS) was prospectively evaluated.RESULTS Fasting blood glucose, insulin, HOMA-IR and HbA 1c(all P 0.0001) levels were higher in non-diabetic CRC patients compared with obesity-matched controls. All parameters were associated with increased CRC risk at ROC analysis, but no relationship with clinical-pathological variables or survival outcomes was observed for glycemia, insulinemia or HOMA-IR. Conversely, advanced CRC stage(P = 0.018) was an independent predictor of increased Hb A1 c levels, which were also higher in patients who had disease progression compared with those who did not(P = 0.05). Elevated Hb A1 c levels showed a negative prognostic value both in terms of PFS(HR = 1.24) and OS(HR = 1.36) after adjustment for major confounders, which was further confirmed in a subgroup analysis performed after exclusion of diabetic patients.CONCLUSION HbA 1c might have a negative prognostic value in CRC, thus suggesting that glycemic metabolic markers should be carefully monitored in these patients, independently of overt diabetes.