C-peptide concentrations in patients with type 2 diabetes treated with insulin

AimsTo determine beta cell reserves of patients with type 2 diabetes who are treated with insulin by using fasting C-peptide concentrations and to investigate the clinical features related to C-peptide concentrations.Materials and methodsPatients with type 2 diabetes, who were using insulin as monotherapy or in combination therapy, were divided into three groups; those with an insufficient beta cell reserve (C-peptide: <0.5 ng/mL), borderline reserve (C-peptide: 0.5–2 ng/mL) and sufficient reserve (C-peptide:> 2 ng/mL).ResultsIn the 249 patients (mean age, 61.77 ± 9.34 years; 40.6% male), the mean duration of diabetes was 13.9 ± 8.43 years. The mean HbA1c concentrations, fasting glucose and C-peptide concentrations were 8.88 ± 1.87%, 184.29 ± 77.88 mg/dL and 1.95 ± 1.37 ng/mL, respectively. Fifty-seven percent of patients (n = 142) had a borderline beta cell reserve and 37% (n = 92) had high C-peptide concentrations. Only 6% of patients (n = 15) had an insufficient beta cell reserve. C-peptide levels were positively correlated with waist circumference (r: 0.282; p = 0.001), hip circumference (r: 0.251; p = 0.001), body mass index (r: 0.279; p = 0.001), fasting glucose concentrations (r: 0.309; p = 0.001) and triglyceride concentrations (r: 0.358; p = 0.001).ConclusionIn this study, almost all patients with type 2 diabetes using insulin were found to have sufficient or borderline beta cell reserves and insulin resistance-related parameters were prominent in those with adequate beta cell reserve.Clinical trials noNCT04005261     

Postprandial serum C-peptide to plasma glucose ratio as a predictor of subsequent insulin treatment in patients with type 2 diabetes

Type 2 diabetes is a progressive disease and most patients with type 2 diabetes eventually need insulin therapy. The objective of this study was to clarify C-peptide immunoreactivity (CPR), a marker of beta cell function, as a predictor of requirement for insulin therapy. We conducted a retrospective study of 579 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007 and were able to be followed up for at least 6 months after discharge. Fasting and postprandial serum CPR and urinary CPR levels had been measured during admission. Information about insulin therapy at the last visit was obtained from medical records. At the last visit, 364 subjects (62.9%) were treated with insulin. Mean interval between discharge and the last visit was 4.5 ± 2.3 years. Serum and urine CPR levels at baseline were significantly associated with insulin treatment at the last visit (P<0.001 for all). Among CPR values, postprandial serum CPR to plasma glucose ratio (CPR index) showed the greatest area under the receiver operating characteristic (ROC) curve for insulin therapy. Multivariate logistic regression analysis evaluating the effect of postprandial CPR index adjusted for other confounders showed consistent results with unadjusted results. In conclusion, beta cell dysfunction is significantly correlated with future insulin therapy in patients with type 2 diabetes. Our study indicates that among CPR measurements, postprandial CPR index is the best predictive marker for future insulin therapy.     

Influence of exogenous insulin on C-peptide levels in subjects with type 2 diabetes

Aim:The aim of this study was to determine whether the influence of insulin therapy on fasting and stimulated C-peptide levels in type 2 diabetic subjects is due to plasma glucose reduction or a direct effect of exogenous insulin.Methods:Plasma glucose and serum C-peptide levels were determined before and after IV injection of 1 mg glucagon on three separate days in 21 type 2 diabetic subjects. Day 1: without pharmacological treatment and fasting plasma glucose >11.1 mmol/L; day 2: fasting plasma glucose 4.4–7.8 mmol/L, 1 h after withdrawing intravenous regular insulin infusion; day 3: fasting plasma glucose 4.4–7.8 mmol/L with bed-time NPH insulin.Results:Fasting and glucagon stimulated C-peptide levels were higher on day 1 than days 2 and 3. Fasting, but not stimulated C-peptide levels, were lower on day 3 than day 2. These differences were not appeared when the percentage of C-peptide increment or the C-peptide/glucose ratio were compared in the three days.Conclusions:Blood glucose reduction instead of exogenous insulin is responsible for the C-peptide decrease during insulin therapy in type 2 diabetic subjects.     

Magnesium deficiency and insulin resistance in patients with type 2 diabetes mellitus

Magnesium is a predominantly intracellular ion, and it is a cofactor in more than 300 enzymatic reactions, like tyrosinokinase activity. Its deficiency may increase insulin resistance, especially in patients with metabolic syndrome or type 2 diabetes. This study evaluated in 27 patients with poorly controlled type 2 diabetes if there was correlation between intracellular magnesium levels, laboratorial indexes of insulin resistance and glycemic control. Decreased serum and intracellular magnesium depletion were found in 75% and 30.8% of patients, respectively. A negative correlation between intracellular magnesium levels (ICMg) and BMI and HbA1 was found. The homeostasis model assessment for insulin resistance (HOMA-IR) was higher than 3.0 in 59.2% of patients and there was a tendency to negative correlation with ICMg levels, although without statistical significance. Despite the small number of patients, this study shows that magnesium deficiency is frequent in patients with diabetes and its correlation with insulin resistance should be more studied.     

Contribution of insulin deficiency and insulin resistance to the development of type 2 diabetes: nature of early stage diabetes

At the time of diagnosis of type 2 diabetes (T2D), patients already have varying degrees of beta-cell dysfunction and insulin resistance and the defects continue to deteriorate despite treatment. We examined insulin secretion impairment and insulin resistance in overweight patients with T2D who had metformin failure, with elevated HbA1c at maximal metformin dose. Patients (N = 1,039) were examined at entry to the European Exenatide (EUREXA) clinical trial of add-on exenatide versus sulphonylurea. Mean (±SD) age was 57 ± 10 years, and BMI was 32.4 ± 4.1 kg/m². All patients underwent an oral glucose tolerance test; HOMA-IR, HOMA-B, ?I ₃₀/?G ₃₀, disposition index and pro-insulin/insulin ratio were evaluated in relation to stratified HbA1c levels (≤7.3, >7.3–8.2, >8.2%) and duration of diabetes (<3, ≥3–<6, ≥6 years) using non-parametric analysis of variance. Patients overall had a wide range of impaired insulin secretion (HOMA-B: median 50.4, interquartile range 32.8–78.8) and insulin resistance (HOMA-IR: 4.8, 3.0–7.4). With increasing HbA1c levels, there was a statistically significant decrease in HOMA-B (P < 0.001), ?I ₃₀/?G ₃₀ (P = 0.003) and disposition index (P < 0.001), and increase in pro-insulin/insulin (P < 0.001) and HOMA-IR (P < 0.001). With increasing duration since diabetes diagnosis, there was a significant decrease in HOMA-B (P < 0.001), but no significant trend in HOMA-IR, ?I ₃₀/?G ₃₀, disposition index or pro-insulin/insulin. Metformin failure in these patients was associated with beta-cell dysfunction to a greater extent than insulin resistance. Loss of the first-phase insulin release, indicated by a low ?I ₃₀/?G ₃₀, would indicate that this patient cohort requires add-on therapy that can maintain beta-cell function.     

脂联素与瘦素的比值和2型糖尿病胰岛素抵抗的相关性

在160例2型糖尿病患者分析脂联素与瘦素的比值(A/L)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)和胰岛素抵抗参数的相关性.结果 显示,在两性患者中,A/L和体重指数、腰臀比、甘油三酯、高密度脂蛋白胆固醇均显著相关.当空腹血糖逐渐升高时,A/L与胰岛素抵抗参数仍然相关,而HOMA-IR不再相关,提示A/L相对于脂联素、瘦素、HOMA-IR是一个较好评估胰岛素抵抗的指标.     

Starting insulin in type 2 diabetes: Overcoming barriers to insulin therapy

BACKGROUND:

Several barriers to insulin therapy are encountered by both the providers and the patients with type 2 diabetes mellitus. These barriers include the fear of the needles i.e. number of injections as well as number of times of self blood glucose monitoring, fear of hypoglycemia and weight gain as well as the convenience, compliance and the cost. However, most of these patients are likely to require insulin therapy with increasing duration of the disorder because of the progressive cell failure. Therefore the most important aspect of insulin therapy must revolve around the regimen most suitable and acceptable because of its ability in overcoming these barriers while being effective in attaining and maintaining desirable glycemic control.

METHODS:

Recently published studies using different regimens with combinations of various oral agents and insulins in patients with type 2 DM and manifesting lapse of glycemic control when treated with various oral agents are discussed. Specific attention is paid to the capacity of each individual regimen in overcoming aforementioned barriers.

RESULTS:

Comparative analysis amongst various insulin regimens shows that combination of metformin, and glimeperide with SC administration of basal insulin Lantus required the least daily dose of insulin with least consequential hypoglycemia as well as weight gain. Moreover, the number of injections as well as the number of times of self blood glucose monitoring, were lesser with this regimen with better compliance and more convenience in comparison to other combination insulin regimens.

CONCLUSION:

The insulin regimen with fewest barriers consists of one SC injection of basal insulin lantus in combination with oral agents. However, to be effective, oral agents must include a secretogogue i.e. glimeperide in addition to a sensitizer i.e. metformin and not multiple sensitizers without a secretogogue. Moreover, this regimen apparently is also the most preferred by the patients, and is cost effective.     

老年2型糖尿病病人血清尿酸/肌酐比值与胰岛素抵抗及胰岛B细胞功能的相关性

目的 探讨老年2型糖尿病(T2DM)病人血清尿酸/肌酐比值(SUA/SCr)与胰岛素抵抗及胰岛B细胞功能的相关性.方法 选择老年T2DM病人784例(男512例,女272例),均行75 g口服葡萄糖耐量试验(OGTT),并测定SUA、SCr、TG、TC、LDL-C、HDL-C、HbA1c、葡萄糖、胰岛素等指标水平,并计...     

Association of C-peptide with diabetic vascular complications in type 2 diabetes

AimFasting serum C-peptide is a biomarker of insulin production and insulin resistance, but its association with vascular complications in type 2 diabetes mellitus (T2DM) has never been fully elucidated. This study aimed to investigate whether C-peptide is associated with cardiovascular disease (CVD) and diabetic retinopathy (DR).MethodsA total of 4793 diabetes patients were enrolled from seven communities in Shanghai, China, in 2018. CVD was defined as a self-reported combination of previous diagnoses, including coronary heart disease, myocardial infarction and stroke. DR was examined using fundus photographs. Logistic regression analyses were performed, and multiple imputed data were used to obtain stabilized estimates.ResultsPrevalence of CVD increased with increasing C-peptide levels (Q1, Q2, Q3 and Q4: 33%, 34%, 37% and 44%, respectively; P_{for trend} < 0.001), whereas DR prevalence decreased with increasing C-peptide quartiles (Q1, Q2, Q3 and Q4: 21%, 19%, 15% and 12%, respectively; P_{for trend} < 0.001). On logistic regression analysis, C-peptide levels were significantly associated with CVD prevalence (1.27, 95% CI: 1.13–1.42; P < 0.001) and C-peptide quartiles (Q1: reference; Q2: 1.31, 95% CI: 1.00–1.70; Q3: 1.53, 95% CI: 1.16–2.01; Q4: 1.76, 95% CI: 1.32–2.34; P_{for trend} < 0.001). Given the interaction between C-peptide and BMI and the association between C-peptide and CVD (P_{for interaction} = 0.015), study participants were divided into two subgroups based on BMI which revealed that the association persisted despite different BMI statuses. However, DR prevalence decreased with increasing C-peptide levels (0.73, 95% CI: 0.62–0.86; P < 0.001) and quartiles (Q1: reference; Q2: 1.00, 95% CI: 0.76–1.33; Q3: 0.69, 95% CI: 0.50–0.94; Q4: 0.51, 95% CI: 0.36–0.72; P_{for trend} < 0.001).ConclusionC-peptide was positively associated with CVD, but inversely associated with DR progression. The association between C-peptide and CVD could be due to associated metabolic risk factors.     

HLA-types,C-peptide and insulin antibodies in juvenile diabetes

Summary HLA-types were determined in 102 juvenile diabetics. HLA-B8 was found in 39 patients (RR 2.64; p < 0.01) and HLA-BW15 in 32 patients (RR 1.33; n.s.). HLA-B7 was found in 14 patients (RR 0.40; p < 0.05). There were no correlations between HLA-B8 or BW15 and family history of diabetes, occurrence of infection before onset of diabetes, ketonuria at onset or the age at onset of diabetes. Serum C-peptide, insulin binding capacity of IgG and total serum insulin, IRI, were determined in 94 patients who had had diabetes for more than two years and who were beyond the remission period. Measurable amounts of C-peptide were found in 33 patients (34.7%). There was no evidence of a relationship between any particular HLA-antigen and the B-cell function except for an increased incidence of detectable C-peptide in patients with HLA-B18 and a tendency to a decreased incidence of detectable C-peptide in patients with the combination HLA-B8, W15. Only four patients (4.3%) were lacking insulin antibodies. HLA-BW15 positive patients had higher levels of insulin antibodies than other groups, while HLA-B7 positive patients had lower levels. The results suggest that HLA-B7 and HLA-B 18 might be associated with a different and perhaps milder form of juvenile diabetes.This work was supported by the Swedish Medical Research Council no 16X-3557 and no 19X-04 528, by the Swedish Diabetic Association and by the Medical Faculty, Linköping University, Sweden     

Low serum creatinine predicts risk for type 2 diabetes

Aims

As an insulin target tissue, skeletal muscle is inversely related to type 2 diabetes mellitus (T2DM). Serum creatinine originates mainly from creatine in muscle and is considered as a reliable surrogate marker for muscle mass in apparently healthy subjects. It is therefore hypothesized that low serum creatinine could effectively predict increased risk of T2DM. Yet information is scarce regarding the longitudinal relationship between serum creatinine and T2DM. This study aims to investigate this relation in a large general population of both men and women.

Methods

A prospective cohort study (n = 57 587; follow‐up range: 1‐9 years, mean: 3.57 years, 95% confidence interval: 3.55‐3.58 years) was conducted in a general population sample from Tianjin, China. Multivariable Cox proportional hazards regression models were used to assess the relationship between baseline serum creatinine and the risk of developing T2DM (as defined by the American Diabetes Association criteria).

Results

During the follow‐up period, 2017 subjects developed T2DM. The multivariate‐adjusted hazard ratios (95% confidence interval) for T2DM incidence across quintiles of serum creatinine were 1.00 (reference), 0.86 (0.75, 0.99), 0.82 (0.72, 0.94), 0.85 (0.74, 0.97), and 0.77 (0.67, 0.89; P for trend <.01). Similar results were observed in both sexes (interaction P = .56).

Conclusions

These findings indicate that serum creatinine concentration is inversely related to incident T2DM in both men and women. Measuring serum creatinine may assist in the early detection of individuals at high risk of developing T2DM.     

Basal insulin treatment in type 2 diabetes

Insulin glargine is the first 24-h recombinant DNA insulin analog introduced to the market. Substitution of glycine for asparagine and addition of two arginine residues raise the isoelectric point of insulin glargine and result in microprecipitates, delaying absorption from subcutaneous tissue. This delayed absorption result in fairly flat 24-h insulin concentration profiles with no discernible peak. Large, multicenter, randomized, controlled trials in patients with type 2 diabetes show that although NPH insulin and insulin glargine are equally effective in lowering glycosylated hemoglobin (A1c) and fasting blood glucose, there is a clear advantage of insulin glargine over NPH insulin in reducing nocturnal and overall hypoglycemia. Lower risk of hypoglycemia with glargine was also consistently demonstrated by trials comparing insulin glargine and premixed analog insulins. These studies also showed greater reduction in A1c with twice-daily premixed insulins compared with glargine, when insulin glargine was administered without mealtime insulin coverage. Insulin glargine was also compared with another insulin analog, insulin detemir. Trials showed that both insulin analogs are equally effective in lowering A1c and have comparable risk of hypoglycemia. Trials comparing insulin glargine with glucagon-like peptide-1 agonists showed comparable significant reductions in A1c with both regimens. Insulin glargine is well tolerated, has low immunogenicity, reduced risks for acute myocardial infarction, and a lower risk of hypoglycemia compared with NPH insulin in individuals with type 2 diabetes.     

Fasting plasma C-peptide,glucagon stimulated plasma C-peptide,and urinary C-peptide in relation to clinical type of diabetes

Summary Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis 40 years, and 4) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients with a fasting plasma C-peptide value <0.20 nmol/l, a glucagon stimulated plasma C-peptide value <0.32 nmol/l, and a urinary C-peptide value <3.1 nmol/l, or <0.54 nmol/mmol creatinine/24 h, or <5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide levels above these values mainly were Type 2. At these limits the percentage, predictive value of positive tests as indicators of Type 2 diabetes were as follows: fasting C-peptide 83%, stimulated C-peptide 86%, and urinary C-peptide expressed as nmol/l 76%, as nmol/mmol creatinine/24 h 79%, and as nmol/24 h 78%. Similarly, the percentage predictive value of negative tests as indicators of Type 1 diabetes were as follows: fasting C-peptide 86%, stimulated C-peptide 88%, and urinary C-peptide expressed as nmol/l 79%, as nmol· mmol creatinine·24 h 81%, and as nmol/24 h 80%. If patients without detectable C-peptide were excluded, the predictive value of negative tests were as follows: fasting C-peptide 81%, stimulated C-peptide 88%, urinary C-peptide expressed as nmol/l 61%, as nmol/mmol creatinine/24 h 69%, and as nmol/24 h 64%. In conclusion, post glucagon C-peptide gives a good distinction between Type 1 and Type 2 diabetes mellitus in insulin treated diabetes while 24 h urinary C-peptide gives a less sensitive distinction between the clinical types of diabetes.