C-peptide and autoimmune markers in diabetes

Autoimmune markers such as islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) and islet antigen-2 antibodies (IA-2A) are found in high frequencies among type 1 patients and especially among younger patients. Presence of these autoantibodies confirms the destructive process of the beta cells associated with immune-mediated type 1 diabetes. Type 2 diabetes is characterised by peripheral insulin resistance and a relative deficiency in insulin production. However, when autoimmune markers are analysed these are found in about 10% of patients clinically classified as type 2 diabetes, indicating that the frequency of type 1 diabetes is underestimated. GADA is the most frequent marker both among patients clinically classified as type 1 and type 2. GADA is also highly predictive for insulin treatment in patients not classified as type 1 diabetes. C-peptide is the best marker of the endogenous insulin production. Sampling of C-peptide is preferably done in the non-fasting condition since these values differentiate better between autoimmune and non-autoimmune diabetes. The presence of autoimmune markers at diagnosis predicts a course of further deteriorating beta cell function, whereas absence of autoimmune markers predicts stable beta cell function for the first two years in adults. Presence of GADA and in particular in high levels are prognostic for a low beta cell function within the next few years after diagnosis. Positivity only for ICA indicates a more preserved beta cell function for the first three years compared to positivity for other autoimmune markers.     

Diabetes, insulin resistance, and the metabolic syndrome in patients with acute myocardial infarction without previously known diabetes

OBJECTIVE: Individuals with diabetes have an increased morbidity from acute myocardial infarction (AMI). Based on an oral glucose tolerance test (OGTT), 40-45% of patients with AMI have diabetes. The objective of this study was to characterize the glucometabolic profile of patients with AMI without known diabetes and to see if sustained glucometabolic perturbations are predictable during the hospital phase of the disease. RESEARCH DESIGN AND METHODS: A total of 145 patients with AMI and no previous diagnosis of diabetes were subjected to an OGTT at hospital discharge and 3 months thereafter. Based on the OGTT after 3 months, they were defined as having normal glucose tolerance (NGT; n = 50), impaired glucose tolerance (IGT; n = 59), or diabetes (n = 36). Components of the metabolic syndrome, including insulin resistance assessed by homeostasis model assessment (HOMA-IR), were recorded. RESULTS: Patients with AMI had no changes in insulin resistance from hospital discharge to follow-up. An OGTT and/or a single blood glucose taken 60 min (BG-60) after ingestion of 75 g glucose at hospital discharge were predictors of the outcome of the OGTT at follow-up. With a cutoff value for BG-60 of 8.6 mmol/l, 70% of the patients were correctly predicted as either belonging to the NGT group or the IGT/diabetes group after 3 months. Age, BMI, antihypertensive treatment, HbA(1c), fasting blood glucose, blood lipids, insulin, proinsulin, HOMA-IR, and plasminogen activator inhibitor 1 did not add predictive power. CONCLUSIONS: Patients with AMI and no previous diagnosis of diabetes have no changes in insulin resistance from hospital discharge to a 3-month follow-up. An OGTT or a single BG-60 performed at hospital discharge predicts the diagnosis of IGT or diabetes 3 months thereafter.     

Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy

OBJECTIVE: To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes. RESEARCH DESIGN AND METHODS: Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy. RESULTS: A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA(1c) were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes. CONCLUSIONS: Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.     

自身抗体筛检隐匿型自身免疫性糖尿病的意义

目的:检测胰岛素自身抗体(IAA)、胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)和血清C肽,筛选出成年隐匿型自身免疫性糖尿病(LADA)对其进行早诊断、早治疗。方法:采用ELISA法检测188例初诊糖尿病患者血清IAA、ICA和GADA,化学发光法检测空腹和餐后C肽。结果:阳性组50例患者中,GADA阳性率(16.0%)高于ICA阳性率(12.2%)和IAA阳性率(7.4%)。双抗体阳性率为6.9%,三抗体阳性率为1.1%。抗体阳性患者的空腹和餐后C肽明显低于抗体阴性患者,双抗体和三抗体阳性患者的空腹和餐后C肽低于单抗体阳性患者。结论:自身抗体阳性患者的胰岛功能明显低于阴性患者。双抗体或三抗体的阳性患者,其胰岛功能丧失的更多。通过三抗体联合检测在初诊糖尿病患者中筛选LADA,对其早诊断早治疗具重要意义。     

High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry

OBJECTIVE: To study the presence and levels of GAD65 antibodies (GADA), IA-2 antibodies (IA-2-A), and islet cell antibodies (ICA) during the first years after clinical onset of type 1 diabetes in relation to age at diagnosis. RESEARCH DESIGN AND METHODS: Type 1 diabetic patients (n = 194) <40 years of age were consecutively recruited at the time of diagnosis by the Belgian Diabetes Registry and followed during the first 4 years of insulin treatment. ICA were determined by indirect immunofluorescence assay and IA-2-A, GADA, and insulin autoantibodies by a radioligand assay. RESULTS: Overall, 94% of initially antibody-positive patients (n = 180) remained positive for at least 1 antibody type 4 years after diagnosis. In the case of diagnosis after 7 years of age, GADA, IA-2-A, and ICA persisted in 91, 88, and 71%, respectively, of the initially antibody-positive patients. Antibody persistence was lower in those diagnosed at <7 years of age, amounting to 60% for GADA, 71% for IA-2-A, and 39% for ICA. In 57% of the initially antibody-positive patients, at least 1 type of autoantibody reached peak values after diagnosis. This occurred more frequently for clinical onset after 7 years of age and more often for GADA (49%) than for IA-2-A (29%) or ICA (19%). Of the patients, 24% that were negative for GADA at onset became GADA-positive during the following 4 years. Among the 7% initially antibody-negative patients, 2 of 14 subjects developed antibodies after clinical onset. CONCLUSIONS: In particular, for diagnosis after 7 years of age, islet cell-specific autoantibodies generally persist for many years after diagnosis. There is also a high frequency of increasing antibody levels and of conversion to antibody positivity in the first 4 years after diagnosis and start of insulin treatment. Thus, determination of antibodies at diagnosis can underestimate the number of cases with autoimmune type 1 diabetes, in particular with assays of lower sensitivity. The divergent temporal patterns of ICA, GADA, and IA-2-A suggest that the ICA test recognizes other antibody specificities besides GADA and IA-2-A and reflects other autoimmune processes; it also indicates that GADA assays have a higher diagnostic sensitivity in the period after clinical onset.     

糖尿病自身抗体联合检测在糖尿病分型中的应用价值研究

目的探讨糖尿病自身抗体联合检测在糖尿病分型中的应用价值,为正确分型糖尿病提供理论依据。方法选择我院内分泌科收治的126例糖尿病患者,其中1型糖尿病组51例,2型糖尿病组75例,同时选择健康对照组60例,采用免疫印迹试剂法检测胰岛细胞抗体（ICA）、胰岛素自身抗体（IAA）和谷氨酸脱羧酶抗体（GADA）表达情况,计算阳性率,并对结果进行比较分析。结果 ICA、IAA和GADA在1型糖尿病患者中的阳性率分别为35.3%、31.4%和60.8%,显著高于2型糖尿病患者的1.3%、1.3%、2.7%及对照组的1.3%、0.0%、0.0%,均有显著性差异（P〈0.05）。ICA/IAA/GADA、GADA/ICA、GADA/IAA三种联合检测组合对1型糖尿病诊断的敏感性分别为92.2%、84.3%和82.4%,均显著高于单一抗体检测,均有显著性差异（P〈0.05）。结论检测血清ICA、IAA和GADA能够为正确鉴别1型糖尿病和2型糖尿病提供重要依据,联合检测能够提高诊断阳性率,避免漏诊,值得临床推广和普及。     

Autoantibodies to a 38-kDa glycosylated islet cell membrane-associated antigen in (pre)type 1 diabetes: association with IA-2 and islet cell autoantibodies.

OBJECTIVE: To study the association of autoantibodies against a 38-kDa glycated islet cell membrane-associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification. RESEARCH DESIGN AND METHODS: Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays. RESULTS: GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for > or = 1 other autoantibody. CONCLUSIONS: GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs.     

T1DM患者直系亲属ZnT-8A、IA-2A、IAA、GADA、ICA检测及3年发病风险分析

目的探讨1型糖尿病(T1DM)患者直系亲属Zn T-8A、IA-2A、IAA、GADA、ICA检测及3年发病风险的临床价值。方法采用放射免疫沉淀法检测T1DM患者(n=80)及其直系亲属(n=100)与正常受试者(n=100)血清中锌转运蛋白8抗体(Zn T-8A)阳性率,同时采用免疫印迹试剂法检测胰岛细胞抗体(ICA)、谷氨酸脱羧酶抗体(GADA)、蛋白酪氨酸磷酸酶自身抗体(IA-2A)、胰岛素自身抗体(IAA),对不同组合抗体联合检测效果用ROC曲线评价,同时分析直系亲属中3年发病情况。结果 T1DM组患者Zn T-8A、IA-2A、IAA、GADA、ICA血清抗体检出率均显著高于直系亲属组和健康组(P0.05),且直系亲属组上述血清抗体检出率显著高于健康组(P0.05)。5种抗体联合检测总阳性率最高为91.25%,其中2种、3种和4种抗体联合总阳性率最高,分别为83.75%、87.5%和90.0%。5种抗体联合检测法的ROC曲线下面积(AUC)最大,各种抗体联合检测法AUC无显著差异,但均显著高于Zn T-8A抗体单独检测(P0.05)。3年随访调查中2例Zn T-8A和GADA抗体阳性直系亲属被诊断为T1DM,其余个体在随访期间无发病症状。结论 5种抗体联合检测能够提高T1DM临床诊断率,其中Zn T-8A和GADA抗体组合检测,对糖尿病及时、准确分型具有重要价值,还可作为T1DM直系亲属流行病学的筛选指标。     

Grave''''s病患者血清IAA、ICA、GADA的测定及意义

目的测定Graves病患者血清中IAA、ICA、GADA的水平并进一步探讨其意义。方法2003-2004年在我院新诊断的c嗍病患者54例，分别测定患者空腹血糖、OGTT 2h血糖，并以ELISA方法测定其血清IAA、ICA、GADA。结果54例Graves病患者中检出糖耐量减退（IGT）患者8例，糖尿病（DM）患者3例。IAA、ICA、GADA阳性率分别为3．7％、9．26％、11．1％。结论ICA、GADA与Graves病有关，但不是病人出现血糖异常的主要原因。     

Antibodies to IA-2 and GAD65 in type 1 and type 2 diabetes: isotype restriction and polyclonality

OBJECTIVE: To determine the isotypes and clonality of antibodies to GAD (GADA) and IA-2 (IA-2A) in patients with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied the following consecutive series of patients who attended a diabetes center for antibodies to GADA and IA-2A: 52 newly diagnosed type 1 diabetic patients, 199 type 2 diabetic patients, 200 control patients, and a cohort of 34 nondiabetic identical twins of patients with type 1 diabetes (15 of whom developed diabetes) who were followed prospectively. RESULTS: GADA or IA-2A were detected in 37 (71%) type 1 diabetic patients compared with only 10 (5%) type 2 diabetic patients (P<0.0001). Both GAD and IA-2 antibodies, regardless of the type of diabetes, were usually subclass restricted to IgG1 and were polyclonal. IgM, IgG3, and IgE isotypes were also detected, but all isotypes of GADA and IA-2A were less prevalent than IgG1 (P<0.017 for either antibody). There was no evidence of spreading or switching of isotypes before the onset of type 1 diabetes. CONCLUSIONS: These observations suggest that the pathogenesis of antigen-specific antibodies in type 1 and type 2 diabetes is similar and probably involves a chronic nonrandom antigen-driven polyclonal B-cell activation that is consistent with a Th1-type immune response.     

探讨糖尿病前期患者血浆IL-18、PAI-1水平变化与胰岛素抵抗的相关性

目的探讨血浆白细胞介素-18(IL-18)、纤溶酶原激活物抑制物-1(PAI-1)水平变化与Ⅱ型糖尿病发病危险因素的关系.方法 设立健康人对照(NGT)组、糖耐量减低( IGT )组、空腹血糖受损合并糖耐量减低(IFG/IGT)组,每组各100例.测定各受试者血浆 IL-18、PAI-1、血清空腹胰岛素、空腹血糖、餐后2 h血糖,应用稳态模型评估法评价胰岛素抵抗(HOMA-IR).结果 IGT组、IFG/IGT组血浆 IL-18、PAI-1 水平均高于NGT组(P<0.01).IFG/IGT组血浆 IL-18、PAI-1 水平均高于IGT组(P<0.05).相关分析显示IL-18、PAI-1 水平与空腹血糖、餐后2 h血糖、HOMA-IR呈正相关(P<0.01).结论血浆 IL-18、PAI-1 水平升高可能是加重糖尿病前期患者胰岛素抵抗的危险因素;在糖尿病前期,IL-18、PAI-1可能参与了Ⅱ型糖尿病的发生、发展.     

Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes. A population-based study. The Childhood Diabetes in Finland Study Group.

An unselected population of 755 siblings of children with insulin-dependent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid decarboxylase (GADA), insulin autoantibodies (IAA), and combinations of these markers. We also evaluated whether the histochemical ICA test could be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or close to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively. In contrast to the other three antibody specificities, GADA levels were not related to the risk for IDDM. The risk for IDDM in siblings with four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8%, respectively. Combined screening for IA-2A and GADA identified 70% of all ICA-positive siblings, and all of the ICA-positive progressors were also positive for at least one of the three other markers. The sensitivity of the combined analysis of IA-2A and GADA was 81%, and the positive predictive value was 41%. In conclusion, combined screening for IA-2A and GADA may replace the ICA assay, giving comparable sensitivity, specificity, and positive predictive value. Accurate assessment of the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with only one or no antibodies initially will progress to IDDM.     

Impaired glucose tolerance in the U.S. population

Impaired glucose tolerance (IGT) constitutes two-thirds of all glucose intolerance in the United States and is a major risk factor for diabetes. Despite these findings, the clinical and epidemiological significance of IGT has not been well investigated. The Second National Health and Nutrition Examination Survey, a cross-sectional study in which 75-g 2-h oral glucose tolerance tests (OGTTs) were performed, has provided an opportunity to examine the characteristics of IGT in the U.S. population. Data from the survey have been extrapolated to represent all U.S. residents. The findings indicate that approximately 11.2% of Americans aged 20-74 yr have IGT compared to 6.6% with diabetes. Rates of IGT increased with age for White men and women and Black men but declined for Black women greater than 54 yr of age, possibly because greater obesity in Black women precipitated earlier conversion of IGT to diabetes. The distribution of 2-h glucose values showed IGT to be part of a continuum of glucose intolerance extending from normal to diabetes. Individuals with IGT had rates of risk factors for non-insulin-dependent diabetes (age, plasma glucose, past obesity, family history of diabetes, physical inactivity) that were intermediate between those of individuals with normal glucose tolerance and those with diabetes, although current obesity was similar for IGT and diabetes. The proportion of people with medical histories of diabetes-related conditions did not differ between IGT and normal glucose tolerance. However, several cardiovascular findings were more prevalent in individuals with IGT than in those with normal glucose tolerance, including hypertension, serum cholesterol, angina, abnormal heart findings, and medical history of arteriosclerosis and stroke. Both obesity and reported family history of diabetes were associated with higher rates of IGT, with the effect of weight gain on the prevalence of IGT occurring at lower levels than for diabetes.     

致动脉硬化指数及血清同型半胱氨酸检测在糖尿病患者冠心病发病风险预测中的应用

目的 探讨致动脉硬化指数(AIP)及血清同型半胱氨酸(Hcy)水平预测2型糖尿病(T2DM)患者发生冠心病的临床价值.方法 选取102例T2DM患者、72例糖耐量减低(IGT)患者,与糖耐量正常(NGT)对照组75例,分别对其糖化血红蛋白(HbA1c)、同型半胱氨酸(Hcy)、脂蛋白(a)[Lp(a)]、超敏C反应蛋白(hs-CRP)以及常规血脂项目进行检测,计算AIP指数.T2DM患者再根据HbA1c的含量又分成血糖控制良好组(HbA1c≤7.0%,n=62)和血糖控制不佳组(HbA1c>7.0%,n=40),并与NGT组进行比较.结果 T2DM组和IGT组血清Hcy、AIP指数显著高于NGT组,差异具有统计学意义(P<0.01或P<0.05);T2DM组与IGT组比较,血清Hcy、Lp(a)、hs-CRP、AIP指数差异均具有统计学意义(P<0.01或P<0.05);血糖控制不佳组(HbA1c>7.0%),其血清Lp(a)、AIP指数明显高于血糖控制良好组(HbA1c≤7.0%),差异有统计学意义(P<0.01),Hcy和hs-CRP也较血糖控制良好组(HbA1c≤7.0%) 升高(P<0.05),并且Hcy、Lp(a)、hs-CRP和AIP指数水平均具有随HbA1c升高而升高的趋势.结论 同时监测AIP指数及血清Hcy、Lp(a)、hs-CRP水平有助于判断糖尿病的发生、发展,相比而言,AIP指数和Hcy水平优于其他动脉粥样硬化指标,可作为IGT及T2DM发生动脉粥样硬化危险性的早期预测指标.     

Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes

OBJECTIVE: Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors. RESULTS: All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA(1c) and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA(1c), which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin. CONCLUSIONS: In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.     

新诊断2型糖尿病患者GADA和ZnT8A自身抗体检测意义研究

目的 分析新诊断2型糖尿病患者中谷氨酸脱羧酶自身抗体(GADA)和锌转运子8自身抗体(ZnT8A)阳性情况。方法 通过ELISA法检测2014年5月～10月收集的101例新诊断2型糖尿病患者血清样本GADA和ZnT8A水平。结果 GADA阳性率为21.78%,ZnT8A阳性率为17.82%,两种自身抗体共同阳性率为8.91%,且GADA和ZnT8A阳性与否与患者的性别(t=-0.724,-0.550; 0.903,1.359,P值均＞0.05)、年龄(r=-0.185,-0.158; 0.367,0.084,P值均＞0.05)、血糖(r=0.290,0.110; -0.264,-0.047,P值均＞0.05)、胆固醇(r=-0.047,0.004; 0.154,-0.138,P值均＞0.05)、三酰甘油(r=-0.092,-0.054; -0.217,-0.023,P值均＞0.05),以及低密度脂蛋白(r=-0.045,-0.027; 0.202,-0.025,P值均＞0.05)水平不存在明显相关性。结论 为了早期诊断成人迟发型自身免疫性糖尿病患者,应该对新诊断的2型糖尿病患者及时进行自身抗体的筛查。     

Alcohol consumption in relation to metabolic regulation, inflammation, and adiponectin in 64-year-old Caucasian women: a population-based study with a focus on impaired glucose regulation

OBJECTIVE: The aims of this study were to examine alcohol drinking patterns in women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) and to investigate whether alcohol intake was associated with improved insulin sensitivity, decreased biomarkers of inflammation, and increased adiponectin levels and if these effects were limited to dysmetabolic women. RESEARCH DESIGN AND METHODS: From a cohort of 64-year-old Caucasian women, 209 with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol consumption and medication use were assessed by questionnaires. Anthropometric data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides, C-reactive protein, white blood cell count, and serum adiponectin were measured. RESULTS: Compared with the NGT group, alcohol consumption was lower in the IGT group and lowest in the diabetes group. Mean alcohol intakes of >9.2 and > or =3-9 g/day were positively associated with adiponectin and insulin sensitivity (homeostasis model assessment [HOMA]), respectively, independently of obesity, metabolic control, and other confounders. Alcohol intake correlated negatively with inflammatory markers, although this did not remain after adjustment for HOMA and waist circumference. The inverse associations between alcohol consumption and factors related to the metabolic syndrome such as HOMA, waist circumference, and inflammatory markers were more obvious among women with diabetes and IGT than in healthy women. CONCLUSIONS: In these women, moderate alcohol consumption showed beneficial associations with the prevalence of type 2 diabetes, IGT, insulin sensitivity, and serum adiponectin. There is a need to clarify whether adiponectin may be a mechanistic link and also to clarify the clinical implications of these observations.     

Reduced insulin secretion in offspring of African type 2 diabetic parents

OBJECTIVE: To determine the early biochemical predictors of increased susceptibility to develop diabetes in offspring of African type 2 diabetic parents. RESEARCH DESIGN AND METHODS: A total of 69 offspring (case subjects) of 26 families in Cameroon with at least one type 2 diabetic parent were studied, and 62 offspring (control subjects) from 25 families in Cameroon with no parent with type 2 diabetes underwent an oral glucose tolerance test. Early insulin secretion was calculated using the ratio of the 0- to 30-min incremental insulin values to the 0- to 30-min incremental glucose. Anthropometric parameters were also measured. RESULTS: Of the case subjects, 23% were glucose intolerant (4% with diabetes and 19% with impaired glucose tolerance [IGT]) compared with 6.5% (all with IGT) of control subjects (P = 0.02). There was also an increasing prevalence of glucose intolerance, especially IGT with increasing number of glucose-intolerant parents. Fasting serum insulin levels were not different in the two groups; however, at 30 min, the case subjects had lower insulin levels than the control subjects (P < 0.006). Case subjects with IGT had lower 30-min insulin concentration, early insulin secretion, and 2-h insulin levels than those with normal glucose tolerance (NGT) (F = 4.1, P < 0.05; F = 4.1, P < 0.04; and F = 5.1, P < 0.03, respectively). Furthermore, case subjects with NGT and IGT had lower early insulin secretion than control subjects (F = 4. 1, P < 0.03). These differences remained after adjustment for BMI and regardless of the status of parental diabetes. Two-hour insulin concentration showed a positive association (odds ratio = 0.95 CI 0.90-0.99, P = 0.039) with IGT in the case subjects. CONCLUSIONS: Diabetes and IGT are more prevalent in the offspring of African type 2 diabetic parents, and this may be due to an underlying degree of beta-cell impairment marked by reduced early-phase insulin secretion.     

Epidemiology of diabetes among Arab Americans

OBJECTIVE: To examine the prevalence of diabetes and glucose intolerance by age and sex in the Arab-American community of Dearborn, Michigan. RESEARCH DESIGN AND METHODS: Participants were randomly selected adult Arab Americans, 20-75 years of age, from randomly selected households in Dearborn, Michigan. Demographic and anthropometric data were recorded. Glucose tolerance was assessed with 2-h 75-g oral glucose tolerance tests and classified according to 1997 American Diabetes Association and 1998 World Health Organization criteria. RESULTS: A total of 626 eligible adults were selected, and 542 participated (87% response rate). Because prevalence increases with age and the overall response rate for women (328/352; 93%) was higher than that for men (214/274; 78%), prevalence rates were adjusted for age and sex. The overall prevalence of diabetes was 15.5% (95% CI 12.2-18.7%) in women and 20.1% (15.0-25.2%) in men (P = 0.13). The prevalence of previously diagnosed diabetes was similar to that of undiagnosed diabetes. Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were present in 16.8% (12.8-20.8%) of women and 29.7% (23.4-35.9%) of men (P = 0.0007). The combined rates of glucose intolerance (diabetes, IGT, and IFG) were 32.3% (27.8-36.7%) for women and 49.8% (43.1-56.4%) for men (P < 0.0001). Among younger adults, the prevalence in men was higher than that in women. As expected, subjects with diabetes or IGT/IFG were older and had greater BMI and waist-to-hip ratios than subjects with normal glucose tolerance. CONCLUSIONS: The prevalence of diabetes and glucose intolerance is extremely high among adult Arab Americans in Michigan and represents a major clinical and public health problem. Community-based intervention programs to prevent and treat diabetes are urgently needed.