Lower Fasting C-peptide Levels Research Articles

Clinical Analysis of 17 Adult Patients With Fulminant Type 1 Diabetes Mellitus

To explore the clinical characteristics of adult patients with fulminant type 1 diabetes mellitus (FT1DM), a specific subtype of type 1 diabetes mellitus (T1DM). We collected the clinical data of patients who were admitted to West China Hospital, Sichuan University in 2010-2019 for FT1DM and type 1 diabetes mellitus (T1DM) presenting with diabetic ketoacidosis (DKA) at the onset. In addition, all the FT1DM patients were followed up. A total of 70 patients presenting with DKA at the onset of T1DM were admitted to and received treatment at West China Hospital in 2010-2019. Among them, 17 (24.3%) had FT1DM and 53 did not. The mean ages of the FT1DM patients and the non-FT1DM patients were (33.2±12.8) years and (27.5±11.2) years, and the mean body mass indices were (22.6±2.9) kg/m 2 and (19.2±2.9) kg/m 2, respectively. A total of 14 FT1DM cases had symptoms of upper respiratory tract infection or acute gastroenteritis before the onset of the disease and 4 cases were related to pregnancy. The median time from the onset of the disease to the first diagnosis of DKA of the FT1DM group (median [P 25-P 75]: 2 [1-4] days, P<0.001) was significantly shorter than that of the non-FT1DM group (median [P 25-P 75]: 30 [17-78] days). The mean maximum blood glucose levels at the time of the first visit to the doctor of the FT1DM patients ([39.9±11.4] mmol/L, P<0.001) were significantly higher than that of the non-FT1DM patients ([28.9±9.2] mmol/L), but the HbA1c (6.6%±0.6%, P<0.001) and glycosylated serum albumin (GA) (21.4%±3.0%, P=0.001) levels of the FT1DM patients were significantly lower than those of the non-FT1DM group (HbA1c: 12.8%±2.7%; GA: 44.8%±15.0%). The median serum amylase in the FT1DM group was significantly higher than that in the non-FT1DM group (101 [54-336] IU/L vs. 54 [42-166] IU/L, P=0.045) and the median serum lipase in the FT1DM group showed a trend of being higher than that in the T1DM group (81 [57-154] IU/L vs. 46 [28-195] IU/L, P=0.051). 8.7% of the non-FT1DM patients tested positive for anti-glutamic acid decarboxylase antibody (GAD-Ab), while the FT1DM patients all tested negative. At the time of discharge, the mean daily insulin dose of the FT1DM patients was (0.67±0.22) IU/kg, which was not significantly different from that of the non-FT1DM group ([0.74±0.29] IU/kg, P=0.349). After about 6.5 years of follow-up, the mean daily insulin dose of the FT1DM patients was (0.73±0.19) IU/kg, which was similar to the insulin dosage on discharge ( P=0.409). Compared with the non-FT1DM patients presenting with DKA at the onset, FT1DM patients have fewer typical diabetic symptoms, lower fasting C-peptide levels, higher serum amylase levels, and increased incidence of vomiting or other symptoms of gastrointestinal infections, and are more likely to be misdiagnosed. Therefore, it is very important for clinicians to correctly identify FT1DM as early as possible and administer early and long-term insulin replacement therapy.

Characteristic phenotype of Chinese patients with adult-onset diabetes who are autoantibody positive by 3-Screen ICA\u2122 ELISA

AimsTo assess the prevalence of diabetes-associated autoantibodies in Chinese patients recently diagnosed with adult-onset diabetes and to evaluate the potential role of the autoantibody markers for characterization of disease phenotype in the patient population.MethodsThe study included 1273 recent-onset adult patients with phenotypic type 2 diabetes mellitus (T2DM). Serum samples were tested using the 3-Screen ICA™ ELISA (3-Screen) designed for combined measurement of GADAb and/or IA-2Ab and/or ZnT8Ab. 3-Screen positive samples were then tested for individual diabetes-associated and other organ-specific autoantibodies. Clinical characteristics of patients positive and negative in 3-Screen were analysed.ResultsForty-four (3.5%) of the T2DM patients were positive in 3-Screen, and 38 (86%) of these were also positive for at least one of GADAb, IA-2Ab and ZnT8Ab in assays for the individual autoantibodies. 3-Screen positive patients had lower BMI, higher HbA1c, lower fasting insulin levels and lower fasting C-peptide levels compared to 3-Screen negative patients. Analysis using a homeostatic model assessment (HOMA2) indicated that HOMA2-β-cell function was significantly lower for the forty-four 3-Screen positive patients compared to 3-Screen negative patients.Twenty (45%) 3-Screen positive patients were also positive for at least one thyroid autoantibody.ConclusionsThe 3-Screen ELISA has been used successfully for the first time in China to detect diabetes autoantibodies in patients with phenotypic T2DM. 3-Screen positive patients presented with poorer β cell function.

Monogenic Diabetes in Youth With Presumed Type 2 Diabetes: Results From the Progress in Diabetes Genetics in Youth (ProDiGY) Collaboration.

OBJECTIVEMaturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis may result in a change in clinical treatment and impacts prediction of complications and familial risk. In this study, we aimed to assess the prevalence of MODY in multiethnic youth under age 20 years with a clinical diagnosis of type 2 diabetes.RESEARCH DESIGN AND METHODSWe evaluated whole-exome sequence data of youth with a clinical diagnosis of type 2 diabetes. We considered participants to have MODY if they carried a MODY gene variant classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines.RESULTSOf 3,333 participants, 93 (2.8%) carried an LP/P variant in HNF4A (16 participants), GCK (23), HNF1A (44), PDX1 (5), INS (4), and CEL (1). Compared with those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 2.5 vs. 13.6 ± 2.3 years, P = 0.002) and lower fasting C-peptide levels (3.0 ± 1.7 vs. 4.7 ± 3.5 ng/mL, P < 0.0001). Youth with MODY were less likely to have hypertension (6.9% vs. 19.5%, P = 0.007) and had higher HDL cholesterol (43.8 vs. 39.7 mg/dL, P = 0.006).CONCLUSIONSBy comprehensively sequencing the coding regions of all MODY genes, we identified MODY in 2.8% of youth with clinically diagnosed type 2 diabetes; importantly, in 89% (n = 83) the specific diagnosis would have changed clinical management. No clinical criterion reliably separated the two groups. New tools are needed to find ideal criteria for selection of individuals for genetic testing.

Donor insulin use predicts beta-cell function after islet transplantation.

Insulin is routinely used to manage hyperglycaemia in organ donors and during the peri-transplant period in islet transplant recipients. However, it is unknown whether donor insulin use (DIU) predicts beta-cell dysfunction after islet transplantation. We reviewed data from the UK Transplant Registry and the UK Islet Transplant Consortium; all first-time transplants during 2008-2016 were included. Linear regression models determined associations between DIU, median and coefficient of variation (CV) peri-transplant glucose levels and 3-month islet graft function. In 91 islet cell transplant recipients, DIU was associated with lower islet function assessed by BETA-2 scores (β [SE] -3.5 [1.5], P = .02), higher 3-month post-transplant HbA1c levels (5.4 [2.6] mmol/mol, P = .04) and lower fasting C-peptide levels (-107.9 [46.1] pmol/l, P = .02). Glucose at 10 512 time points was recorded during the first 5 days peri-transplant: the median (IQR) daily glucose level was 7.9 (7.0-8.9) mmol/L and glucose CV was 28% (21%-35%). Neither median glucose levels nor glucose CV predicted outcomes post-transplantation. Data on DIU predicts beta-cell dysfunction 3 months after islet transplantation and could help improve donor selection and transplant outcomes.

Longitudinal association of biomarkers of pesticide exposure with cardiovascular disease risk factors in youth with diabetes

BackgroundCardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. ObjectivesTo describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. MethodsPesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. ResultsParticipants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: −0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of −0.64 (−1.17, −0.11) for 2,4-D and −0.39 (−0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (−0.11, 3.01) higher and log FCP levels that were −0.28 (−0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. ConclusionsExposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes.

Fasting C-peptide, a biomarker for hypoglycaemia risk in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL.

To examine the relationship between baseline fasting C-peptide (FCP) and outcomes in insulin-naïve people with type 2 diabetes initiating basal insulin glargine 100 U/mL (Gla-100). Post hoc pooled analysis of nine randomized, treat-to-target trials in patients with type 2 diabetes inadequately controlled on oral antihyperglycaemic drugs initiating once-daily Gla-100. Participants (n = 2165) were stratified at baseline according to FCP (≤0.40, >0.40-1.20, >1.20-2.00, >2.00 nmol/L). Glycaemic control, body weight, insulin dose and hypoglycaemia were determined at 24 weeks. At baseline low FCP levels were associated with longer known diabetes duration, lower body mass index and higher fasting plasma glucose (FPG). Following Gla-100 introduction, the mean HbA1c reduction at week 24 was similar in all four FCP groups, albeit fewer people in the lowest FCP group achieved HbA1c <7.0% versus FCP groups >0.40 nmol/L. By contrast, FPG reduction and proportion reaching FPG ≤5.6 mmol/L were greatest in the lowest FCP group, diminishing at higher FCP levels. Gla-100 dose at week 24 was lowest in the ≤0.40 nmol/L FCP group and highest in the >1.20 nmol/L FCP group. Incidence and event rate of overall, nocturnal and severe hypoglycaemia were higher at week 24 in groups with lower FCP levels. In multivariable regression analysis baseline FCP, concomitant sulphonylurea use and endpoint HbA1c were strong predictors of hypoglycaemia. FCP levels identified patients with type 2 diabetes experiencing different responses to basal insulin Gla-100. A low FCP identifies a markedly insulin-deficient, insulin-sensitive subgroup/phenotype with an enhanced risk of hypoglycaemia, which requires a low initial basal insulin dose, cautious titration and earlier addition of prandial glucose-lowering therapy.

Identification of Novel T1D Risk Loci and Their Association With Age and Islet Function at Diagnosis in Autoantibody-Positive T1D Individuals: Based on a Two-Stage Genome-Wide Association Study.

Type 1 diabetes (T1D) is a highly heritable disease with much lower incidence but more adult-onset cases in the Chinese population. Although genome-wide association studies (GWAS) have identified >60 T1D loci in Caucasians, less is known in Asians. We performed the first two-stage GWAS of T1D using 2,596 autoantibody-positive T1D case subjects and 5,082 control subjects in a Chinese Han population and evaluated the associations between the identified T1D risk loci and age and fasting C-peptide levels at T1D diagnosis. We observed a high genetic correlation between children/adolescents and adult T1D case subjects (r g = 0.87), as well as subgroups of autoantibody status (r g ≥ 0.90). We identified four T1D risk loci reaching genome-wide significance in the Chinese Han population, including two novel loci, rs4320356 near BTN3A1 (odds ratio [OR] 1.26, P = 2.70 × 10-8) and rs3802604 in GATA3 (OR 1.24, P = 2.06 × 10-8), and two previously reported loci, rs1770 in MHC (OR 4.28, P = 2.25 × 10-232) and rs705699 in SUOX (OR 1.46, P = 7.48 × 10-20). Further fine mapping in the MHC region revealed five independent variants, including another novel locus, HLA-C position 275 (omnibus P = 9.78 × 10-12), specific to the Chinese population. Based on the identified eight variants, we achieved an area under the curve value of 0.86 (95% CI 0.85-0.88). By building a genetic risk score (GRS) with these variants, we observed that the higher GRS were associated with an earlier age of T1D diagnosis (P = 9.08 × 10-11) and lower fasting C-peptide levels (P = 7.19 × 10-3) in individuals newly diagnosed with T1D. Our results extend current knowledge on genetic contributions to T1D risk. Further investigations in different populations are needed for genetic heterogeneity and subsequent precision medicine.

Monogenic Diabetes in the Progress for Diabetes Genetics in Youth (ProDiGY) Collaboration

Monogenic diabetes, including maturity-onset diabetes of the young (MODY), is frequently misdiagnosed as type 1 or type 2 diabetes. Correct diagnosis can result in a change in clinical treatment and impacts prediction of complications and familial risk. Clinical algorithms can select individuals for genetic testing; however, up to half of youth with MODY do not meet clinical criteria. Other barriers also limit access to genetic testing. To assess the prevalence of MODY in youth with a clinical diagnosis of type 2 diabetes, we evaluated whole-exome sequence data from ProDiGY, a collaboration of the TODAY, SEARCH for Diabetes in Youth, and T2D-GENES studies. Focusing on 14 genes previously identified as causal for MODY (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, KCNJ11, ABCC8, and APPL1) we considered patients to have MODY if they carried one or more variants classified as likely pathogenic (LP) or pathogenic (P) according to current guidelines. We found 77 of 3650 patients carried an LP/P variant in HNF4A (14 individuals), GCK (22), HNF1A (32), PDX1 (4), INS (3), and PAX4 (2). Compared to those with no LP/P variants, youth with MODY had a younger age at diagnosis (12.9 ± 0.3 vs. 13.6 ± 0.1, P=0.01) and lower fasting C-peptide levels (3.0 ± 0.2 vs. 4.5 ± 0.1, P=0.0001), although for both measures, the range of values overlapped between the two groups. Youth with MODY were less likely to have hypertension (6.9% vs. 18.2%, P=0.03) and less likely to be on insulin (32.0% vs. 51.1%, P=0.001). Parental history of diabetes was not significantly different. MODY was found in all race/ethnic groups. Using a comprehensive set of MODY genes, we identified MODY in 2% of youth with clinically diagnosed type 2 diabetes; in 88% (n=68) the specific diagnosis would direct management. While these individuals differed significantly on several clinical characteristics, no criterion reliably separated the two groups. Further study is needed to find ideal criteria to select individuals for genetic testing. Disclosure J. Todd: None. J.W. Kleinberger: None. S. Srinivasan: None. S.E. Tollefsen: None. L.L. Levitsky: Consultant; Self; Eli Lilly and Company. L.E.L. Katz: None. J.B. Tryggestad: None. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. G. Imperatore: None. J.M. Lawrence: None. C. Pihoker: None. J. Divers: None. J. Flannick: None. D. Dabelea: None. J.C. Florez: Consultant; Self; Intarcia Therapeutics, Inc.. Consultant; Spouse/Partner; Santen. T.I. Pollin: Research Support; Self; Regeneron Pharmaceuticals, Inc..

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody

BackgroundLatent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes.MethodsWe included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics.ResultsThe prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups.ConclusionThe prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results.

Diabetes incidence in childhood and youth is increasing worldwide, including autoimmune and non-autoimmune cases. Recent findings suggest that there is a larger than expected proportion of type 2 diabetes in youth, and potential cases of intermediate diabetes phenotypes. Most pediatric diabetes registries focus on type 1 diabetes. Also, there is an absence of reliable data on type 2 diabetes incidence in youth. The DiMelli study aims to establish a diabetes incidence cohort registry of patients in Germany, diagnosed with diabetes mellitus before age 20 years. It will be used to characterize diabetes phenotypes by immunologic, metabolic, and genetic markers. DiMelli will assess the contribution of obesity and socio-demographic factors to the development of diabetes in childhood and youth. Recruitment of patients started in 2009, and is expected to continue at a rate of 250 patients per year. 84% of the 216 patients recruited within the first year were positive for multiple islet autoantibodies, 12% for one islet autoantibody, and 4% were islet autoantibody-negative. Patients with multiple islet autoantibodies were younger and had lower fasting C-peptide levels, compared to islet autoantibody-negative patients (median age 10.0 vs. 14.1 years, p < 0.01). Results from the first year of the study show that DiMelli will help to reveal new knowledge on the etiology of diabetes, and the contribution of genetic predisposition and environmental risk factors to the different types of diabetes.

Plasma C-peptide level is inversely associated with family history of type 2 diabetes in Korean type 2 diabetic patients

Type 2 diabetes is characterized by progressive β-cell dysfunction. Family history of type 2 diabetes has been known to be associated with an increased risk for the development of the disease. However, few studies have evaluated the effects of family history of diabetes on residual β-cell function in type 2 diabetic patients. We investigated associations among family histories, clinical characteristics and plasma C-peptide levels in type 2 diabetic patients. A total of 1,350 patients with type 2 diabetes were recruited. The patients with a family history of type 2 diabetes had younger age at onset of diabetes, longer diabetes duration, higher LDL-cholesterol, and lower fasting C-peptide levels than the patients without family history. When divided according to the tertiles of diabetes duration, patients with a family history of type 2 diabetes had more decreased concentrations of fasting C-peptide as duration of diabetes increased, but patients without a family history did not. Multiple regression models were used to determine the association between fasting plasma C-peptide levels and a family history of type 2 diabetes mellitus. With adjustments for age and sex, glycated hemoglobin (HbA(1C)), fasting plasma glucose, free fatty acids, body mass index and diabetes mellitus (DM) duration, there was a significant association (P < 0.01). Our results showed that a family history of diabetes was significantly associated with the progressive decline of fasting plasma C-peptide levels in Korean type 2 diabetes mellitus.

Comparison of the effects of polysulfone and polyester-polymer alloy dialyzers on glycemic control in diabetic patients undergoing hemodialysis

Though different high-flux dialyzers are available, there are no comparative studies on their glycemic control effects on diabetic hemodialysis (HD) patients. In this crossover study, we compared the effects of polysulfone (PS) and polyester-polymer alloy (PEPA) dialyzers. We recruited 47 diabetic HD patients. The conventional dialyzers were replaced with PS or PEPA dialyzers and the patients were treated for 16 weeks. Subsequently, after interchanging the PS and PEPA dialyzers, the treatment continued for another 16 weeks. For each dialyzer, we analyzed the glycemic control effect and measured their clearance and reduction rates of insulin. The PEPA dialyzer lowered the glycated albumin (GA) levels more significantly than the PS dialyzer. While the groups exhibited no differences in metabolic parameters, the clearance and reduction rates of insulin were more significant in the PS. A significant decrease was observed in the levels of GA, fasting plasma glucose, and glycated hemoglobin in patients with lower fasting C-peptide levels (< 6.0 ng/ml). Glycemic control in diabetic HD patients is affected by the type of dialyzer used. Our results indicate that the PEPA dialyzer is more potent in controlling glycemia than the PS dialyzer in diabetic HD patients.

Heterogeneity of Patients With Latent Autoimmune Diabetes in Adults: Linkage to Autoimmunity Is Apparent Only in Those With Perceived Need for Insulin Treatment

OBJECTIVE—Subjects with the diagnosis of latent autoimmune diabetes in adults (LADA) are more prone to need insulin treatment than those with type 2 diabetes. However, not all patients with LADA develop the need for insulin treatment, indicating the heterogeneity of LADA. We investigated this heterogeneity by comparing phenotypes of LADA with and without perceived need for insulin treatment (data obtained at times when diagnosis of LADA was not investigated) and also compared LADA and type 2 diabetes phenotypes.RESEARCH DESIGN AND METHODS—We used data from the all population–based Nord-Trøndelag Health study (n = 64,931), performed in 1995–1997. Data were assembled for individuals with LADA (n = 106) and type 2 diabetes (n = 943).RESULTS—In the comparison of individuals with LADA both with and without the need for insulin, insulin-treated subjects had higher titers of GAD antibodies (P < 0.001) and lower fasting C-peptide levels (P < 0.001). GAD antibodies and C-peptide correlated negatively (r = −0.40; P = 0.009). In the comparison of individuals with LADA and type 2 diabetes, all without the need for insulin, markers of metabolic syndrome were equally prevalent and pronounced. Age, C-peptide, and glucose levels were also similar. In the comparison of insulin-treated individuals with LADA and type 2 diabetes, more patients with LADA received insulin (40 vs. 22%, P < 0.001) and C-peptide levels were lower (P < 0.001). Patients with LADA were leaner but were still overweight (mean BMI 28.7 vs. 30.9 kg/m2 in type 2 diabetes, P < 0.001). In the comparison of type 2 diabetic patients with and without insulin, insulin-treated subjects were more obese and had higher A1C and lower C-peptide levels (P < 0.001).CONCLUSIONS—Our conclusions are that 1) the need for insulin treatment in LADA is linked to the degree of autoimmunity and β-cell failure, 2) subjects with LADA and type 2 diabetes without the need for insulin treatment are phenotypically similar, and 3) insulin treatment in type 2 diabetic patients is associated with both insulin resistance and β-cell insufficiency.

Plasma lipoproteins, apoproteins and cardiovascular disease in Type 2 diabetic patients. A nine-year follow-up study

Background and Aim: To evaluate the role of lipoprotein abnormalities as risk factors for macroangiopathy in Type 2 diabetes. Methods and Results: This prospective nine-year follow-up study involved 113 Type 2 diabetic patients (50 men and 63 women, mean age 66.9±9.9 years), 37 of whom had clinical signs of coronary heart disease (CHD) and cerebrovascular disease (CVD) at baseline. During the follow-up, 32 patients died: 17 of CHD, five of CVD, and 10 of non-vascular causes. The patients who died because of vascular disease were more frequently smokers, and had baseline symptoms of vascular disease; they were also significantly different from the other patients insofar as they were older, and had higher fasting plasma glucose levels, lower fasting C-peptide levels, and lower apoprotein (apo) AII, apo CII, apo CIII and apo E levels. Univariate analysis showed that baseline symptoms of vascular disease, current smoking, age, high fasting plasma glucose levels, low fasting C-peptide levels, and low apo AII, apo CII, apo CIII and apo E levels [but not cholesterol, triglyceride, high-density lipoprotein (HDL)-cholesterol or qualitative low-density lipoprotein or HDL abnormalities were associated with cardiovascular mortality. Multivariate analysis showed that only age, smoking, glycated hemoglobin (HbA 1c) and fasting C-peptide levels were significant independent determinants of macrovascular death. Conclusions: In Type 2 normolipidemic diabetic patients, only age, smoking, HbA 1c and fasting C-peptide levels are independent vascular risk factors. The differences in apo concentrations between patients with and without vascular disease may reflect qualitative abnormalities in plasma lipoproteins related to vascular disease.

Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population.

Fasting serum insulin and fasting serum C-peptide are risk factors for developing type 2 diabetes. Because of the higher incidence of type 2 diabetes in African Americans and Hispanic Americans, it is likely that these groups may differ from non-Hispanic whites in their levels of insulin and C-peptide. We analyzed data from a nationally representative sample of adults in the US population for whom sociodemographic, clinical, and laboratory information were obtained. The data were used to describe distributions of fasting insulin and fasting C-peptide in non-Hispanic white, non-Hispanic black, and Mexican American men and women aged >or=20 years without a medical history of diabetes. Among men, Mexican Americans had higher insulin values than non-Hispanic whites and blacks. Among women, both Mexican Americans and blacks had higher insulin values than whites. For C-peptide, differences by sex and race-ethnicity paralleled those seen for fasting insulin with the exception that black men had significantly lower C-peptide values than whites and Mexican Americans. After adjustment for age, fasting plasma glucose (FPG), body mass index (BMI), and waist-to-hip ratio (WHR), the higher levels for insulin in blacks and Mexican Americans remained; both black men and women had significantly lower C-peptide values than whites and Mexican Americans. The molar ratio of fasting C-peptide to fasting insulin was similar for men and women in each race-ethnic group. However, blacks had substantially lower ratios than whites and Mexican Americans. We found wide variations in fasting insulin and fasting C-peptide levels by race and ethnicity in US adults that were not explained by confounding factors, primarily measures of obesity. Most notably, the higher fasting insulin and lower fasting C-peptide levels in blacks implies that there is a derangement in insulin clearance and an impairment in beta-cell function in blacks compared with whites and Mexican Americans.