Postprandial C-peptide Levels Research Articles

Prevalence and influencing factors of pulmonary nodules in hospitalized patients with diabetes.

Pulmonary nodules are an early manifestation of many lung cancers, and patients with diabetes are at high risk for lung cancer. However, there is a lack of epidemiological data on pulmonary nodules in patients with diabetes. This study investigated the prevalence rate of pulmonary nodules in hospitalized patients with diabetes and analyzed its influencing factors, with the aim of generating data to inform the management of pulmonary nodules in patients with diabetes. This retrospective study included 1,864 patients with diabetes admitted to the Department of Endocrinology and Metabolism in the North District of Suzhou City Hospital from January 2020 to November 2022. According to the chest computed tomography (CT) examination, the patients were divided into two groups: a no pulmonary nodules group and a pulmonary nodules group. The prevalence rate of pulmonary nodules was calculated, and the number, size, nature, and other imaging characteristics of pulmonary nodules were compared. The pulmonary nodule group was divided into three subgroups according to the following nodule diameters: <5, ≥5 and <10, and ≥10 and ≤30 mm. The clinical data, blood biochemistry, insulin resistance index, and serum tumor marker levels were recorded. A multinomial logistic regression model was used to analyze the influencing factors of pulmonary nodule in diabetic patients. Among the 1,864 hospitalized patients with diabetes, 1,407 were found to have pulmonary nodules, representing a total prevalence rate of 75.48%. Compared with the pulmonary nodules subgroups, the no pulmonary nodules group had a higher proportion of males, a lower smoking rate, and higher incidence of proteinuria (all P values <0.05). Compared with the group with a nodule diameter ≥5 and <10 mm and that with a nodule diameter ≥10 and ≤30 mm, the no pulmonary nodules group had a lower age, insulin use rate, and homocysteine (Hcy) levels but higher fasting and 2-hour postprandial C-peptide level, low-density lipoprotein cholesterol (LDL-C) level and insulin resistance index [Homeostatic Model Assessment for Insulin Resistance 2 (HOMA2IR)] (all P values <0.05). The usage rate of dipeptidyl peptidase 4 (DPP4) inhibitor in the no pulmonary nodules group was lower than that in the subgroup with a nodule diameter ≥5 and <10 mm (P<0.05). Multinomial logistic regression analysis showed that age, smoking, and use of DPP4 inhibitors were independent risk factors for pulmonary nodules. DPP4 inhibitors increased the risk of nodules ≥5 and <10 mm in size, while older age and smoking increased the risk of nodules ≥5 mm in size (all P values <0.05). The prevalence of pulmonary nodules in hospitalized patients with diabetes is up to 75.48%. Older age, smoking, and use of DPP4 inhibitors were found to be independent risk factors for pulmonary nodule development in diabetic patients.

Effects of ginseng berry saponins from panax ginseng on glucose metabolism of patients with prediabetes: A randomized, double-blinded, placebo-controlled, crossover trial

BackgroundPrediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects. PurposeThis study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy. Study design and methodsIn this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed. ResultsCompared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study. ConclusionsAmong prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000).

Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Short chain fatty acids (SCFA) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched short chain fatty acids (BSCFA), isobutyrate, isovalerate, and methylbutyrate, is largely unknown. In a cohort of 219 non-Hispanic Whites and 126 African Americans, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, lipid traits, and other SCFA. We observed a bimodal distribution of BSCFA, with 25 individuals having high levels (HBSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared to the L-BSCFA group (16% versus 49%, P=0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFA. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose were lower and disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial Cpeptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

A randomized double-blind phase Ib clinical trial of SY-009 in patients with type 2 diabetes mellitus

IntroductionSY-009 produces a hypoglycemic effect via inhibiting sodium/glucose cotransporter 1 (SGLT1) in type 2 diabetes mellitus (T2DM) patients. This randomized, double-blind, placebo-controlled, and multiple-dose escalation clinical trial aimed to evaluate the pharmacokinetic and pharmacodynamical characteristics as well as the safety and tolerability of SY-009 in T2DM patients. MethodFifty T2DM patients were randomized into experimental and placebo groups, and hospitalized for 9 days managed with a unified diet and rest management. Subjects were given SY-009 or placebo from day 1 to day 7 at different frequencies and dosages. Single dose cohort was defined as the first dose on day 1 and multiple dose cohort included all the dose from day 1 to 7. Blood samples were collected for pharmacokinetic analysis. Mixed meal tolerance tests were performed. Blood samples were collected to determine glucose, C-peptide, insulin, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP). ResultsPK parameters were not obtained because blood SY-009 concentrations were below the limit of quantitation in all subjects. SY-009 decreased the postprandial glucose. Blood glucose was controlled within 4 hours after taking the drug. Short-term administration of SY-009 (7 days) had no significant effects on fasting glucose but reduced the secretion of C-peptide, insulin, and GIP and increased GLP-1 secretion. The most common adverse event was gastrointestinal disorder manifesting abdominal pain, diarrhea, and bloating. ConclusionPlasma exposure of SY-009 and its metabolites was fairly low in T2DM patients at doses of 1.0-4.0 mg. SY-009 reduced postprandial glucose, C-peptide, and insulin levels, showing relative safety and tolerability in the dose range of 1.0–4.0 mg. Trials RegistrationClinicalTrials.gov Identifier: NCT04345107.

Circulating levels of all proglucagon-derived peptides are differentially regulated postprandially by obesity status and in response to high-fat meals vs. high-carbohydrate meals

We measured all proglucagon-derived peptides (PGDPs) levels in response to administration of three mixed meal tolerance tests (MMTs), examining differences in postprandial PGDP responses in subjects with leanness and obesity or between high-fat vs. high carbohydrate meals. We designed three physiology interventional studies, administering MMTs over a 180-min period to individuals without diabetes after an overnight fast. In Study 1, a 450kcal MMT was administered to n=4 normal weight and n=9 individuals with obesity. In Study 2, a 600kcal high-fat MMT was administered to n=15 normal-weight and n=15 individuals with obesity. In Study 3, n=32 participants with obesity were assigned to receive a 600-kcal high-fat (n=15) or an isocaloric high-carbohydrate MMT (n=17). Fasting and postprandial levels of c-peptide and PGDPs (proglucagon, GLP-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]) were assessed. In study 1, individuals with normal weight displayed elevated glicentin postprandial secretion compared with people with obesity (p=0.002). Following a high-fat MMT with 33% higher energy content in study 2, all postprandial PGDPs levels were elevated (p-time<0.001), irrespective of weight status. In study 3, a prolonged postprandial upregulation of PGDPs during the high-fat MMT was observed in contrast with the acute, short-term (max 60min) PGDP responses to a high-carbohydrate MMT (p-time∗meal<0.001). Across both studies 2 and 3, the postprandial responses of glucagon and MPGF were higher in subjects with male sex whereas glicentin was higher in subjects with female sex. Fat and carbohydrate content of a meal can substantially affect the postprandial levels of PGDPs. Circulating levels of PGDPs are influenced by the energy content of the meal, and additionally, the presence of leanness or obesity affects circulating levels of select PGDPs. These results, which are to be confirmed by additional studies, expand our understanding of PGDP physiology in leanness and obesity. GOV REGISTRATION NUMBERS: (NCT04170010, NCT04430946, NCT04575194).

Type 2 Diabetes Family History as a Significant Index on the Clinical Heterogeneity Differentiation in Type 1 Diabetes.

Family history of type 2 diabetes (T2D) is an important but neglected parameter; however, its role in identifying the heterogeneity and subtypes of type 1 diabetes (T1D) remains unclear. We investigated the effect of family history of T2D on the clinical phenotype of T1D patients and evaluated its value in T1D classification. A total of 1410 T1D patients were enrolled in this prospective study. Information on family history of T2D in first-degree relatives (FDRs) was collected by research nurses using a semi-structured questionnaire as previously described. The effect of family history of T2D on clinical characteristics was evaluated in overall and subgroups of T1D patients stratified by islet autoantibodies, onset age, and human leukocyte antigen (HLA) genotype. Cluster analysis was performed to identify family history of T2D-related subgroups. A total of 10% (141/1410) of patients had at least 1 FDR diagnosed with T2D. A milder phenotype associated with family history of T2D was present in overall T1D patients, including older onset age (P < .001), higher body mass index (P < .001), higher fasting and postprandial C-peptide levels (all P < .01), lower positive rates of all islet autoantibodies, and susceptible HLA genotypes (all P < .05). Clinical heterogeneity associated with family history of T2D in the T1D subgroup stratified by autoimmunity, age of onset, and HLA genotypes was consistent. Using family history of T2D as a cluster variable, T1D patients were divided into 5 clusters, and patients in the T2D family history cluster displayed a milder phenotype than others. Family history of T2D should be considered as an important indicator for precise subclassification of T1D patients based on clinical heterogeneity.

The genetic and clinical characteristics of WFS1 related diabetes in Chinese early onset type 2 diabetes

Diabetes is one of the most common phenotypes of Wolfram syndrome owing to the presence of the variants of the WFS1 gene and is often misdiagnosed as other types of diabetes. We aimed to explore the prevalence of WFS1-related diabetes (WFS1-DM) and its clinical characteristics in a Chinese population with early-onset type 2 diabetes (EOD). We sequenced all exons of the WFS1 gene in 690 patients with EOD (age at diagnosis ≤ 40 years) for rare variants. Pathogenicity was defined according to the standards and guidelines of the American College of Medical Genetics and Genomics. We identified 33 rare variants predicted to be deleterious in 39 patients. The fasting [1.57(1.06–2.22) ng/ml] and postprandial C-peptide levels [2.8(1.75–4.46) ng/ml] of the patients with such WFS1 variations were lower than those of the patients without WFS1 variation [2.09(1.43–3.05) and 4.29(2.76–6.07) respectively, ng/ml]. Six (0.9%) patients carried pathogenic or likely pathogenic variants; they met the diagnostic criteria for WFS1-DM according to the latest guidelines, but typical phenotypes of Wolfram syndrome were seldom observed. They were diagnosed at an earlier age and usually presented with an absence of obesity, impaired beta cell function, and the need for insulin treatment. WFS1-DM is usually mistakenly diagnosed as type 2 diabetes, and genetic testing is helpful for individualized treatment.

Circulating levels of proglucagon-derived peptides are differentially regulated by the glucagon-like peptide-1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6-month long interventional study.

To investigate the changes of circulating levels of all proglucagon-derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment. Seventeen patients with obesity or with overweight and co-morbidities, but without diabetes, were assigned to receive once-daily oral naltrexone/bupropion 32/360 mg (n = 8) or once-daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3-month visits, participants underwent a 3-hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C-peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance-assessed liver steatosis and ultrasound-assessed liver stiffness were measured at each visit. Both medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight-independent increase in the levels of proglucagon (P < .001) and decreases in glucagon-like peptide-2 (GLP-2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon-like peptide-1 (GLP-1) levels in a weight-independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP-2 and glucagon (P < .01). PGDP levels at the 3-month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat-free mass, at both the 3- and 6-month visits. PGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP-1), and future studies should explore whether the addition of other PGDPs (e.g. GLP-2) could offer additional benefits.

Comparison of therapeutic effect of metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus in obese patients

To evaluate the therapeutic effects of two therapeutic strategies based on metformin hydrochloride/vildagliptin and liraglutide on type 2 diabetes mellitus (T2DM) in obese patients. We retrospectively collected the clinical data of 107 obese patients (BMI>25 kg/m2) with T2DM treated in Second Affiliated Hospital of Wannan Medical College (Wuhu, China) during 2019-2021, including 53 patients treated continuously with metformin hydrochloride/vildagliptin and 54 with liraglutide for 3 months. The changes in BMI, waist circumference, fasting blood glucose (FBG), postprandial blood glucose, HbA1C, fasting C-peptide, postprandial C-peptide, fasting insulin and postprandial insulin of the patients after treatment were compared between the two groups. In both of the groups, the patients all showed significant reductions of BMI, waist circumference, FBG, postprandial blood glucose and HbA1C (all P < 0.05) with improved fasting and postprandial C-peptide levels after the treatments (P < 0.05). The two treatment regimens showed comparable blood glucoselowering effects, but liraglutide produced better effect in reducing waist circumference (P < 0.01). Neither of two regimens obviously affected insulin level of the patients (P>0.05). Both metformin hydrochloride/vildagliptin and liraglutide have good therapeutic effects on T2DM in obese patients and can achieve good blood glucose and weight control, but liraglutide has a better effect for weight control.

The average 30-minute post-prandial C-peptide predicted diabetic retinopathy progress: a retro-prospective study

BackgroundThe conclusion between Connecting peptide (C-peptide) and diabetic chronic complication was controversial. The purpose of this study is to explore the possible association between average C-peptide with diabetic retinopathy (DR) progression in Chinese patients with type 2 diabetes.MethodsThis is a retro-prospective study. 622 patients with type 2 diabetes were included. DR was evaluated using non-mydriatic fundus photography and DR progression was defined as any deterioration of either eye. Fasting and postprandial c-peptide levels were assayed at baseline and follow-up period. Differences between continuous variables were compared using the Mann–Whitney U test; and categorical variables were analyzed by the chi-square test. Correlation between parameters and 30-minute postprandial C-peptide were determined by Spearman correlation test. The relationship between C-peptide and DR progression was evaluated by multivariable binary logistic regression. Two-tailed P-values < 0.05 were regarded as statistically significant.ResultsDR was present in 162 (26.0%) patients at baseline, and 26.4% of patients were found progression of DR at follow-up. Patients with progression of DR had lower average levels of 30-minute postprandial C-peptide (2.01 ng/ml vs. 2.6 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (3.17 ng/ml vs. 3.92 ng/ml, p < 0.029), as well as average increment of 30-minute (0.41 ng/ml vs. 0.64 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (1.48 ng/ml vs. 1.93 ng/ml, p < 0.017), than those without DR aggravation. Multivariate logistic regression analysis determined that 30-minute postprandial C-peptide and its increment were related to reduced odds ratios for DR progression (odds ratios [OR] = 0.83 and 0.74, respectively).ConclusionOur results suggest that the Average 30-minute post-prandial C-peptide and increment were negatively correlated with DR progression, which further demonstrates the importance to preserve β-cell residual function in the prevention for DR progression.Trial registrationNot applicable.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas.

To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

Effect of Gplife Advance Diabetic Support on Time in Range in Type 2 Diabetes Mellitus Patients: A Case Report

This case report documents 20 patients suffering from uncontrolled type 2 diabetes mellitus, presenting complaints of fluctuating blood glucose levels. The parameters like fasting and postprandial blood glucose, HbA1c and C- peptide levels of patients were evaluated. These patients were then advised an adjuvant therapy of Gplife advanced diabetic support tablets along with their daily insulin injections. After 60 days of treatment, the therapy was discontinued, and patients were subjected to continuous glucose monitoring for 8 days and time in range (TIR) percentage was calculated. Also, the fasting and postprandial blood glucose, HbA1c and C-peptide levels were estimated. The average TIR percentage was found to be 93.2%, whereas the time above range (TAR) and time below range (TBR) was 6.8 % and 0 % respectively, which indicates that the patients had a negligible incidence of hyper and hypoglycemia after 60 days of treatment. There was a significant decrease by 61 % in HbA1c levels, 40.05 % in fasting blood glucose levels and 34.29 % in postprandial blood glucose levels (p&lt;0.001). C-peptide levels increased by 1.38 folds after 60 days of treatment. Also, there were no evidence of diabetic comorbidities. Thus, indicating a marked improvement in the diabetic condition and overall quality of life in patients.

Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets

Human pluripotent stem cell-derived islets (hPSC islets) are a promising alternative to primary human islets for the treatment of insulin-deficient diabetes. We previously demonstrated the feasibility of this approach in nonhuman primates; however, the therapeutic effects of hPSC islets can be limited by the maladaptive processes at the transplantation site. Here, we demonstrate successful implantation of hPSC-derived islets in a new transplantation site in the abdomen, the subanterior rectus sheath, in eight nonhuman primates (five male and three female). In this proof-of-principle study, we find that hPSC islets survive and gradually mature after transplantation, leading to improved glycemic control in diabetic primates. Notably, C-peptide secretion responds to meal challenge from 6 weeks post-transplantation (wpt), with stimulation indices comparable to those of native islets. The average post-prandial C-peptide level reaches approximately 2.0 ng ml-1 from 8 wpt, which is five times higher than the peak value we previously obtained after portal vein infusion of hPSC islets and was associated with a decrease of glycated hemoglobin levels by 44% at 12 wpt. Although additional studies in larger cohorts involving long-term follow-up of transplants are needed, our results indicate that the subanterior rectus sheath supports functional maturation and maintenance of hPSC islets, suggesting that it warrants further exploration as a transplantation target site in the context of for hPSC-based cell-replacement therapies.

Difference in the early clinical course between children with type 1 diabetes having a single antibody and those having multiple antibodies against pancreatic β-cells.

Islet-cell associated antibodies are predictive and diagnostic markers for type 1 diabetes. We studied the differences in the early clinical course of children with type 1 diabetes with a single antibody and those with multiple antibodies against pancreatic β-cells. Sixty-seven children with type 1 diabetes aged less than 15 years diagnosed between 2010 and 2021 were included in the study and subdivided into two subgroups: children who were single positive for either glutamic acid decarboxylase (GAD) antibodies (n = 16) or insulinoma-associated antigen-2 (IA-2) antibodies (n = 13) and those positive for both antibodies (n = 38) at diagnosis. We compared the patients' clinical characteristics, pancreatic β-cell function, and glycemic control during the 5 years after diagnosis. All clinical characteristics at diagnosis were similar between the two groups. One and two years after diagnosis, children who tested positive for both antibodies showed significantly lower postprandial serum C-peptide (CPR) levels than those who tested positive for either GAD or IA-2 antibodies (p < 0.05). In other periods, there was no significant difference in CPR levels between the two groups. There was a significant improvement in glycosylated hemoglobin (HbA1c) levels after starting insulin treatment in both groups (p < 0.05), but no significant difference in HbA1c levels between the groups. Residual endogenous insulin secretion may be predicted based on the number of positive islet-cell associated antibodies at diagnosis. Although there are differences in serum CPR levels, optimal glycemic control can be achieved by individualized appropriate insulin treatment, even in children with type 1 diabetes.

Factors associated with high glucose variability in patients with type 1 diabetes

BACKGROUND: High glucose variability (GV) is recognized as a risk factor for vascular diabetic complications and hypoglycemia. Factors affecting GV in patients with diabetes needed to be clarified.AIM: To determine the factors associated with high GV in adult patients with type 1 diabetes.MATERIALS AND METHODS: We conducted a single center cross-sectional observational study. In-patients with type 1 diabetes aged 18 to 65 years on basal bolus insulin therapy were included. Day-time and nocturnal Coefficient of Variation (CV), Mean Amplitude of Glycemic Excursions (MAGE), Mean Absolute Glucose (MAG) were calculated from continuous glucose monitoring data. The values of CV, MAGE, MAG within the upper quartile were considered high.RESULTS: The study included 400 individuals, including 111 on continuous subcutaneous insulin infusion (CSII). Patients with high GV had lower fasting and postprandial C-peptide levels and higher insulin doses. According to ROC analysis, daily insulin dose &gt;0.69 U/kg and estimated glomerular filtration rate (eGFR) ≥90.5 ml/min×1.73 m2 were associated with high nocturnal CV values. Dose of basal insulin &gt;0.292 U/kg and bolus insulin &gt;0.325 U/day were associated with nocturnal MAGE. Body mass index (BMI) ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, HbA1c ≥8.3%, eGFR ≥89.5 ml/ min×1.73m2 increased risk of high MAG at night. High day-time CV values were associated with daily insulin dose ≥0.675 U/kg and daily dose of BI ≥0.286 U/kg. The risk of high MAGE was increased with HbA1c ≥8.24% and basal insulin dose ≥0.286 U/kg. BMI ≤23.2 kg/m2, waist circumference ≤80.5 cm, daily insulin dose ≥0.69 U/kg, daily dose of bolus and basal insulin ≥0.325 and ≥0.29 U/kg respectively, and HbA1c ≥8.33% were the risk factors for high day-time MAG. Patients on CSII had lower MAGE (p&lt;0.001) and MAG (p=0.008) compared to those on multiple daily injections.CONCLUSION: In type 1 diabetes, high GV is associated with undetectable residual insulin secretion, normal or reduced body weight, preserved kidney function, supraphysiological doses of insulin, and non-target HbA1c. Patients on CSII have a lower GV than those on multiple daily injections.

Efficacy and safety of oral insulin versus placebo for patients with diabetes mellitus: A systematic review and meta-analysis.

Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2). Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed. Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: -1.94, 95% CI: -3.20 to -0.68, I² = 91.81, P &lt; 0.005) and mean IAA levels (SMD:-0.49, 95% CI: -0.82 to -0.16, I² = 27.12, P &lt; 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported. Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects.

Low levels of postprandial C-peptide are clinically significant in non-proliferative diabetic retinopathy and diabetic macular oedema in Iraqi patients with type 2 diabetes

Objective: To evaluate if the low postprandial C-peptide levels are clinically significant and would it relate to the risk of diabetic retinopathy (DR) in Iraqi patients with type 2 diabetes. Methods: Forty-one patients with diabetes (28 male, 13 female) were included, and eight non-diabetic tests were present in this study: HbAlc and 2 h. Post-prandial C-peptide levels were measured in all patients and control groups. Results: In subjects both NPDR and DMO, patients with DR showed lower levels of postprandial C-peptide and higher HbA1c percent. Regression analysis between postprandial C-peptide and DR showed that postprandial C-peptide was negatively associated with DR with odds ratio: (0.569, CI: 0.370- 0.872, p = 0.01) in Iraqi type 2 diabetes. Conclusion: Low postprandial C-peptide levels may predict NPDR and DMO in T2DM patients. Measuring the postprandial or non-fasting C peptide level offers uncomplicated and flexible testing for an outpatient or inpatient.

The relation between residual β-cell function and autoimmune status in long-term type 1 diabetes patients

Objective: We aimed to investigate the autoimmune status of long-term type 1 diabetes mellitus (T1DM) patients with residual β-cell function. Methods: The residual β-cell function of long-term (disease duration≥10 years) autoimmune T1DM patients from the T1DM Integrated Management Clinic of the Second Xiangya Hospital was assessed by serum C-peptide levels. Patients with fasting or 2-hour postprandial C-peptide levels over the lower sensitivity limit of detection (16.7 pmol/L) were grouped as C-peptide-positive, and others were grouped as C-peptide-negative. We screened and enrolled all the C-peptide-positive patients (n=19). C-peptide-negative patients with matched sex, age, duration, BMI (n=19) and healthy controls (n=19) were recruited at the same time. The frequencies of CD4+T cell (Th1/Th2/Th17/Treg) and B cell (MZB/FoB/B10) subsets, the expression of PD-1/PD-L1 on T and B lymphocytes, and the levels of T1DM related cytokines including IFN-γ, TNF-α, IL-1β, IL-1RA, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-23 and IP-10 were tested. We compared these parameters in patients with different levels of β-cell function. Results: In healthy controls, C-peptide-negative and C-peptide-positive patients, the frequencies M (Q1, Q3) of Th1 cells were 9.93% (7.45%, 15.20%), 14.90% (11.70%, 18.00%) and 10.20% (6.93%, 15.80%) (P=0.015), and the frequencies M (Q1, Q3) of Treg cells were 3.52% (2.92%, 5.68%),2.88% (1.64%, 3.22%) and 3.12% (2.81%, 4.81%) (P=0.005), and the frequencies M(Q1,Q3) of PD-1+B cells were 4.69% (2.64%, 6.37%), 2.11% (1.45%, 3.63%) and 4.20% (2.53%, 6.01%) (P=0.003), respectively. The levels of IL-6 M(Q1,Q3)were 26.43(18.06, 33.35) ng/L, 42.97 (25.52, 66.30) ng/L, and 22.07 (14.85, 34.45) ng/L (P=0.006), and the levels of IP-10 M(Q1,Q3) were 107.39 (76.19, 126.07) ng/L, 188.82 (131.27, 348.18) ng/L and 128.26 (114.31, 136.50) ng/L (P<0.001) in healthy controls, C-peptide-negative and C-peptide-positive patients, respectively. Compared with C-peptide-positive patients, the frequency of Th1 cells and the levels of IL-6 and IP-10 cytokines were higher, while the frequencies of Treg cells and PD-1+B cells were lower in C-peptide-negative patients (all P<0.05). Conclusions: Long-term T1DM patients with residual β-cell function had lower frequency of Th1 cells, lower levels of IL-6, IP-10 cytokines, and higher frequencies of Treg and PD-1+B cells, which indicated a pronounced autoimmune tolerance.

Insulin Requirement and Complications Associated With Serum C-Peptide Decline in Patients With Type 1 Diabetes Mellitus During 15 Years After Diagnosis

ObjectiveC-peptide is conventionally used in assessing pancreatic function in patients with diabetes mellitus. The clinical significance of this molecule during the course of type 1 diabetes mellitus (T1DM) has been recently revisited. This study aimed to investigate the natural course of C-peptide in T1DM patients over the period of 15 years and analyze the association between the residual C-peptide and diabetes complications.MethodsThis retrospective study included a total of 234 children and adolescents with T1DM. Patient data including sex, age at diagnosis, anthropometric measures, daily insulin dose, serum HbA1c, post-prandial serum C-peptide levels, lipid profiles, and diabetic complications at the time of diagnosis and 1, 3, 5, 10, and 15 years after diagnosis were retrospectively collected.ResultsAmong the 234 patients, 101 were men and 133 were women, and the mean patient age at initial diagnosis was 8.3 years. Serum C-peptide decreased constantly since the initial diagnosis, and showed a significant decline at 3 years after diagnosis. At 15 years after diagnosis, only 26.2% of patients had detectable serum C-peptide levels. The subgroup with older patients and patients with higher BMI standard deviation score showed higher mean serum C-peptide, but the group-by-time results were not significant, respectively. Patients with higher serum C-peptide required lower doses of insulin and had fewer events of diabetic ketoacidosis.ConclusionSerum C-peptide decreased consistently since diagnosis of T1DM, showing a significant decline after 3 years. Patients with residual C-peptide required a lower dose of insulin and had a lower risk for diabetic ketoacidosis.

Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes.

Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, the potential associations of insulin resistance (IR) and beta-cell function (BCF) with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood. A cross-sectional survey of 15,928 participants was conducted. Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF. A restricted cubic spline (RCS) nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids. High triglyceride (TG), low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol (LDL-C) accounted for 49.7%, 47.8%, and 59.2% of the participants, respectively. In multivariable analysis, high IR was associated with an increased risk of high TGs ( P for trend <0.001) in T1DM and is associated with an elevated risk of high TG and low HDL-C (all P for trend <0.01) in T2DM. Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders. High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients, suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.