Serum C-peptide Concentrations Research Articles

A four-week dietary intervention with mycoprotein-containing food products reduces serum cholesterol concentrations in community-dwelling, overweight adults: A randomised controlled trial

BackgroundSubstituting dietary meat and fish for mycoprotein, a fungal-derived food source rich in protein and fibre, decreases circulating cholesterol concentrations in laboratory-controlled studies. However, whether these findings can be translated to a home-based setting, and to decrease cholesterol concentrations in overweight and hypercholesterolemic individuals, remains to be established. ObjectiveWe investigated whether a remotely-delivered, home-based dietary intervention of mycoprotein-containing food products would affect various circulating cholesterol moieties and other markers of cardio-metabolic health in overweight (BMI >27.5 kg·m-2) and hypercholesterolaemic (>5.0 mmol·L-1) adults. MethodsSeventy-two participants were randomized into a controlled, parallel-group trial conducted in a free-living setting, in which they received home deliveries of either meat/fish control products (CON; n=39; BMI 33±1 kg·m-2; 13 males, 26 females) or mycoprotein-containing food products (MYC; n=33; BMI 32±1 kg·m-2; 13 males, 20 females) for 4 weeks. Fingertip blood samples were collected and sent via postal service before and after the dietary intervention period and analysed for concentrations of serum lipids, blood glucose and c-peptide. ResultsSerum total cholesterol concentrations were unchanged throughout the intervention in CON, but decreased by 5±2% in MYC (from 5.4±0.2 to 5.1±0.2 mmol·L-1; P<0.05). Serum low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol concentrations were also unchanged in CON, but decreased in MYC by 10±3% and 6±2% (both by 0.3±0.1 mmol·L-1; P<0.05). Serum high-density lipoprotein cholesterol and free triglyceride concentrations were unaffected in CON or MYC. Post-intervention, MYC displayed lower mean blood glucose (3.7±0.2 versus 4.3±0.2 mmol·L-1) and c-peptide (779±76 vs. 1064±86 pmol·L-1) concentrations (P<0.05) vs. CON. ConclusionsWe show that a home-based dietary intervention of mycoprotein-containing food products effectively lowers circulating cholesterol concentrations in overweight, hypercholesterolemic adults. This demonstrates that mycoprotein consumption is a feasible and ecologically valid dietary strategy to improve markers of cardio-metabolic health in an at-risk population under free living conditions. Clinical trial registrationNCT04773483 (https://classic.clinicaltrials.gov/ct2/show/NCT04773483)

Maternal fasting serum C-peptide concentrations in the first and second trimesters and subsequent risk of gestational diabetes mellitus: A nested case-control study among Chinese women

ObjectiveTo examine the association of serum connecting peptide (C-peptide) concentrations with gestational diabetes mellitus (GDM) risk among Chinese women. MethodsA nested case-control study was conducted on 436 reproductive-aged women, involving 218 GDM cases and 218 controls matched at 1:1 by maternal age, in Beijing, China between January 2016 and December 2017. Fasting serum C-peptide were successively determined at 10–14 and 15–20 weeks of gestation. Restricted cubic spline and logistic regression analyses were utilized, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive capacity of C-peptide for GDM. ResultsFasting serum C-peptide concentrations exhibited a significant decrease from the initial to the subsequent trimester in females with normal glucose tolerance (NGT). For each 1 log ng/mL increase of fasting serum C-peptide during the first and second trimesters, GDM risk increased by 2.38-fold [odds ratio (OR): 2.38, 95% confidence intervals (95%CI): 1.33–4.40] and 3.07-fold (OR: 3.07, 95%CI: 1.49–6.62), respectively. The areas under the ROC curves for the first- and second-trimester C-peptide were 80.4% and 82.4%. ConclusionOur findings revealed a positive correlation between fasting serum C-peptide during the first and second trimesters and the risk of GDM or its subtypes, underscoring the potential of C-peptide as a predictor for GDM development.

Insulin Resistance Is Better Estimated by Using Fasting Glucose, Lipid Profile, and Body Fat Percent Than by HOMA-IR in Japanese Patients with Type 2 Diabetes and Impaired Glucose Tolerance: An Exploratory Study.

Aims: The aim of the present study is to estimate insulin resistance (IR) using clinically available parameters except for serum insulin or C-peptide concentration to overcome the limitation of homeostasis model assessment of IR (HOMA-IR), which has been widely used in clinical practice. Patients and Methods: Fifty-two admitted patients with type 2 diabetes or impaired glucose tolerance were enrolled, and steady state plasma glucose (SSPG) method and cookie meal tolerance test were performed together with fasting blood sampling and anthropometric measurements. Insulin sensitivity measured by SSPG was estimated as glucose clearance corrected by the excretion of glucose into urine (C-GC). Results: Log-transformed (C-GC) was negatively correlated with fasting plasma glucose (FPG), log (Fasting triglyceride: TG), log (Fasting TG/Fasting high-density lipoprotein cholesterol: HDLC), and their area under the curves (AUCs). Fasting and AUC-HDLC was positively and fasting free fatty acid (FFA) was negatively correlated with log (C-GC). Body fat (%) was negatively correlated with log (C-GC). Multiple regression analysis on log (C-GC) as an outcome variable revealed that FPG, log (AUC-TG/AUC-HDLC), body fat (%), and fasting FFA were selected as significant predictive variables and contributed to log (C-GC) by 60% (adjusted R2). Replacing log (AUC-TG/AUC-HDLC) with its fasting value, log (Fasting TG/Fasting HDLC), this model still showed a strong contribution to log (C-GC) by 57% (adjusted R2). These contributions were stronger than those in log (HOMA-IR) (52.5%), log (Fasting C-peptide) (45.7%) to log (C-GC). Conclusions: It is plausible that our estimation for IR without the inclusion of plasma insulin concentration can be applied in Japanese patients whose HOMA-IR is not appropriately available. The model using fasting values is less complicated and could be the best way for the estimation of IR.

Effects of Betaine and Kaempferol On some criteria related to glucose homeostasis in Methionine Over Load Rats -part 2

This study was designed to evaluate the role of Kaempferol(KPF) and Betaine (BET) in attenuating deleterious effects of methionine overload on some parameters related to diabetes in rats. Thirty (30) adult rats were randomly selected and divided equally into five experimental groups and treated for 45 days as the follows: G1:Rats in this group served as control, Rats in all other groups (G2,G3,G4 and G5 were received 100mg/kg B.W of D-L methionine in drinking water, and received orally as follows: Rats in group G3 were given 150 mg/kg b.w. of KPF, rats in group G4were given 250 mg/kg b.w. BET, rats in group G5 were given 150 mg/kg b.w. of KPF , 250 mg/kg b.w. BET. Fasting blood sample were collected by cardiac puncture technique at the end of the experiments and serum were collected for estimation glycemic indices,. C-peptide and B12 concentration. The results of the experiment that showed given D-L methionine for 45 days(G2group) caused disturbance in glycemic indices as detected by elevation in serum glucose and decrease in serum insulin hormone concentration) and decrease in serum C-peptide and B12 concentration. While oral intubation of KPF and BET or their combination caused correction of all recorded parameters.

Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects.

To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference. This was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022. After administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR10%max≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated. The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile. Clinicaltrials.gov, identifier NCT04975022.

Insulinoma with peripheral neuropathy: a case report

BackgroundInsulinomas are rare neuroendocrine tumors that typically present with hypoglycemic crises. Peripheral neuropathy is an uncommon complication of insulinoma. Most clinicians expect peripheral neuropathy symptoms to reverse completely after the insulin-secreting tumor is resected, but this may be a misassumption.Case reportWe report a case of a 16-year-old Brazilian boy with clonic muscle spasms of the lower limbs for almost one year. Disabling paraparesis and confusional episodes had progressively set in as well. There were no sensorial abnormalities in the lower limbs, upper limbs or cranial nerves. An electromyography revealed a motor neuropathy of the lower limbs. The diagnosis of insulinoma was established as serum insulin and C-peptide concentrations were inappropriately normal during spontaneous episodes of hypoglycemia. Following a normal abdominal magnetic resonance scan, the imaging work-up continued with an endoscopic ultrasound, which localized the tumor at the pancreatic body-tail transition. Once localized, a prompt surgical removal (enucleation) of the tumor was undertaken, leading to an immediate and complete resolution of hypoglycemia. The time length between the onset of symptoms and tumor resection was 15 months. After surgery, the symptoms of peripheral neuropathy of the lower limbs showed a slow and only partial improvement. At a two-year follow-up after surgery, although being able to lead a normal and productive life, the patient still reported symptoms of reduced muscular strength in the lower limbs and a new electroneuromyography analysis showed chronic denervation and reinnervation in the legs’ muscles—indicating chronic neuropathic injury.ConclusionThe events of this case reinforce the importance of an agile diagnostic work-up and spry definitive treatment for patients with this uncommon disease, enabling the cure of neuroglycopenia before permanent bothersome complications ensue.

Importance of residual insulin secretion in type 1 diabetes

Finland has the highest incidence of type 1 diabetes in the world, which has led to many important studies of type 1 diabetes in the Finnish population and to the formation of several study groups. In The Lancet Diabetes & Endocrinology, Minna Harsunen and colleagues 1 Harsunen M Haukka J Harjutsalo V et al. Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analyses. Lancet Diabetes Endocrinol. 2023; (published online June 5.)https://doi.org/10.1016/S2213-8587(23)00123-7 Google Scholar present longitudinal and cross-sectional analyses of random C-peptide (an index of insulin secretion and β-cell function) measurements in three Finnish cohorts: 957 newly diagnosed patients seen at Helsinki University Hospital, in collaboration with the Finnish Pediatric Diabetes Registry (FPDR), for the longitudinal analysis; and 3984 study participants from the FinnDiane study group and 645 from the DIREVA regional diabetes registry in western Finland for the cross-sectional analysis. Data from these studies were used to examine which parameters were associated with residual insulin secretion. Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analysesAlthough children with multiple autoantibodies and HLA risk genotypes progressed to absolute insulin deficiency rapidly, many adolescents and adults had residual random serum C-peptide decades after the diagnosis. Polygenic risk of type 1 and type 2 diabetes affected residual random serum C-peptide. Even low residual random serum C-peptide concentrations seemed to be associated with a beneficial complications profile. Full-Text PDF

Residual insulin secretion in individuals with type 1 diabetes in Finland: longitudinal and cross-sectional analyses

Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, many individuals with type 1 diabetes have circulating C-peptide years after the diagnosis. We studied factors affecting random serum C-peptide concentration in individuals with type 1 diabetes and the association with diabetic complications. Our longitudinal analysis included individuals newly diagnosed with type 1 diabetes from Helsinki University Hospital (Helsinki, Finland) with repeated random serum C-peptide and concomitant glucose measurements from within 3 months of diagnosis and at least once later. The long-term cross-sectional analysis included data from participants from 57 centres in Finland who had type 1 diabetes diagnosed after 5 years of age, initiation of insulin treatment within 1 year from diagnosis, and a C-peptide concentration of less than 1·0 nmol/L (FinnDiane study) and patients with type 1 diabetes from the DIREVA study. We tested the association of random serum C-peptide concentrations and polygenic risk scores with one-way ANOVA, and association of random serum C-peptide concentrations, polygenic risk scores, and clinical factors with logistic regression. The longitudinal analysis included 847 participants younger than 16 years and 110 aged 16 years or older. In the longitudinal analysis, age at diagnosis strongly correlated with the decline in C-peptide secretion. The cross-sectional analysis included 3984 participants from FinnDiane and 645 from DIREVA. In the cross-sectional analysis, at a median duration of 21·6 years (IQR 12·5-31·2), 776 (19·4%) of 3984 FinnDiane participants had residual random serum C-peptide secretion (>0·02 nmol/L), which was associated with lower type 1 diabetes polygenic risk compared with participants without random serum C-peptide (p<0·0001). Random serum C-peptide was inversely associated with hypertension, HbA1c, and cholesterol, but also independently with microvascular complications (adjusted OR 0·61 [95% CI 0·38-0·96], p=0·033, for nephropathy; 0·55 [0·34-0·89], p=0·014, for retinopathy). Although children with multiple autoantibodies and HLA risk genotypes progressed to absolute insulin deficiency rapidly, many adolescents and adults had residual random serum C-peptide decades after the diagnosis. Polygenic risk of type 1 and type 2 diabetes affected residual random serum C-peptide. Even low residual random serum C-peptide concentrations seemed to be associated with a beneficial complications profile. Folkhälsan Research Foundation; Academy of Finland; University of Helsinki and Helsinki University Hospital; Medical Society of Finland; the Sigrid Juselius Foundation; the "Liv and Hälsa" Society; Novo Nordisk Foundation; and State Research Funding via the Helsinki University Hospital, the Vasa Hospital District, Turku University Hospital, Vasa Central Hospital, Jakobstadsnejdens Heart Foundation, and the Medical Foundation of Vaasa.

Abstract LB142: Metabolically defined body size phenotypes in relation to subsequent colorectal cancer risk

Abstract Overweight and obesity have been linked to increased risk of several diseases, including colorectal cancer, but the underlying mechanisms are not fully known. An earlier study analyzed metabolically defined body size phenotypes in relation to colorectal cancer risk, using combinations of C-peptide (a marker of insulin resistance) and body mass index (BMI). Higher serum C-peptide concentrations were associated with higher colorectal cancer risk in both overweight and normal weight individuals compared to individuals with low levels of C-peptide and normal weight. The aim of the present study was to see if these results could be replicated and to further explore the role of metabolism and body size phenotypes in colorectal cancer subtypes. We conducted a nested case-control study of 1010 individuals with colorectal cancer and 1010 individually matched (age, sex, cohort, year of blood sampling and data collection, number of freeze-thaw cycles of plasma samples and fasting status at blood sampling) control participants from the population-based Northern Sweden Health and Disease Study. The blood samples and data used in our analyses were collected at a mean of 9.7 years prior to case diagnosis. Participants were categorized as (1) metabolically healthy/normal weight (BMI &amp;lt; 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI &amp;lt; 25 kg/m2), or (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2), where metabolically healthy was defined as C-peptide in the lowest tertile, as in the previous study. We used multivariable conditional logistic regression to calculate odds ratios and confidence intervals and adjusted for tobacco smoking, recreational physical activity and alcohol consumption as potential confounders. In our preliminary results, metabolically unhealthy/overweight individuals had a significantly higher risk of developing colorectal cancer compared to metabolically healthy/normal weight individuals (adjusted odds ratio =1.44, 95% CI 1.13-1.85). The odds ratio for metabolically unhealthy/normal weight individuals was 1.23 (95% CI 0.92-1.65) and for metabolically healthy/overweight individuals 1.23 (95% CI 0.89-1.70). These results support the potential of a more nuanced analysis of metabolism and body size to better understand their etiological contribution to colorectal cancer development. To gain more knowledge about how the role of metabolism and body size might differ between tumor subtypes, we will also analyze body size phenotypes in relation to subtypes of colorectal cancer based on anatomical tumor site, KRAS and BRAF mutations and microsatellite instability status of the tumor. Citation Format: Linda Vidman, Simon Knekta, Björn Gylling, Carl Zingmark, Anna Löfgren-Burström, Richard Palmqvist, Sophia Harlid, Bethany Van Guelpen. Metabolically defined body size phenotypes in relation to subsequent colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB142.

Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus.

This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after mixed-meal tolerance test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes. We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30-T60-T90-T120, 30-120 min after ingestion of mixed-meal) (n=168). Fasting C-peptide concentrations (in n=535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C-peptide secretion and the correspondence of C-peptide at MMTT T90 / T120 and total AUC were assessed. A total of 153 participants (25%) had detectable fasting serum C-peptide (i.e ≥ 3.8pmol/L). Fasting C-peptide was significantly lower at Year 1 (p < 0.001, effect size=-0.16). Participants with higher fasting C-peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non-detectable fasting and post-meal serum C-peptide concentrations. The T90 and T120 C-peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C-peptide was only detectable at MMTT and not in the fasting state. Stimulated C-peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C-peptide at 1-year follow-up.

Corosolic acid improves glucose and insulin responses in middle-aged men with impaired fasting glucose: A randomized, double-blinded, placebo-controlled crossover trial

• Corosolic acid (CA) improved glucose tolerance in healthy, hyperglycemic individuals. • CA intake (1 mg/d) for 2 weeks improved postprandial glucose and insulin sensitivity. • CA improved the liver insulin sensitivity index after glucose loading. • CA intake did not alter gastrointestinal hormone levels or appetite measures. Corosolic acid (CA) improves glucose metabolism in diabetics and prediabetics, but its effects in healthy subjects with borderline hyperglycemia are unclear. Non-diabetic middle-aged men (n = 14) with impaired fasting glucose tolerance (mean ± SD; age, 51.7 ± 9.0 years; fasting blood glucose, 6.0 ± 0.4 mmol/L) underwent an oral glucose tolerance test (OGTT) after taking 1 mg/d CA or placebo for 2 weeks in a randomized double-blind crossover trial. In the 13 subjects who completed the study, the incremental area under the curve (iAUC) of plasma glucose after the OGTT was significantly lower in the CA condition than in the placebo condition (p = 0.028). The AUC and iAUC of the serum insulin and C-peptide concentrations, and liver insulin sensitivity values were also significantly lower in the CA condition. Glucagon, glucagon-like peptide-1, gastric inhibitory peptide, and non-esterified fatty acid levels did not differ significantly between conditions. CA may improve glucose tolerance in both healthy and prediabetic subjects. Trial registration: UMIN-CTR; http://www.umin.ac.jp/ ; Registration No. UMIN000034130.

Association of Serum C-Peptide with the Components of Metabolic Syndrome among Non Diabetic Obese

Background: Obesity is a major health concern and is associated with metabolic syndrome that increases the risk for cardiovascular disease and diabetes mellitus. C-peptide or connecting peptide, is a short polypeptide that connects A-chain of insulin to its B-chain in the proinsulin molecule. In different studies it was found that C-peptide level are associated with Metabolic Syndrome and its complication. C-peptide is also reported to be more reliable than insulin as a measure of endogenous insulin secretion, insulin resistance and pancreatic beta cell function. The aim of the study is to observe the association of C-peptide levels with the components of metabolic syndrome in non diabetic obese subjects.&#x0D; Materials and methods: This was a hospital based cross- sectional study comprising hundred non diabetic apparently healthy obese subjects age between 30-70 years. This study was carried out at the Department of Biochemistry and Outpatient Department of endocrinology, Chittagong Medical College Hospital. Samples were collected by non-probability convenient sampling. &#x0D; Results: Serum C-peptide was significantly higher in Metabolic Syndrome positive subjects (4.29 ±0.28 ng/ml) than non-Metabolic Syndrome (1.72 ± 0.12ng/ml). There was significant association between Metabolic Syndrome and increased serum C-peptide concentration. Serum Cpeptide levels were significantly associated and positively correlated with serum triglyceride, blood pressure, fasting plasma glucose and negatively correlated with HDL-C in the cases.&#x0D; Conclusion: However, this study did not find any significant association between WC (Waist Circumference) or HDL and Serum C-peptide concentration. Higher Cpeptide level was associated with the components of Metabolic Syndrome and BMI (obesity) was the most important factor affecting the C-peptide concentration to develop Metabolic Syndrome.&#x0D; JCMCTA 2022 ; 33 (1) : 148-153

Accidental exposure to glimepiride from adulterated medication resulting in severe hypoglycaemia.

SummarySulphonylureas are insulinotropic and are not only useful in patients with diabetes but also act in non-diabetic individuals where hypoglycaemia and hyperinsulinism mimic insulinoma. We present a 63-year-old man who presented with inadvertent sulphonylurea-induced life-threatening hypoglycaemia on two occasions, resulting in hazardous and invasive investigation. Biochemistry revealed endogenous hyperinsulinaemia, with elevated serum c-peptide and insulin concentrations during symptomatic hypoglycaemia, and plasma glucose of 1.7 mmol/L. There was no history of sulphonylurea use prompting anatomical insulinoma studies to locate an insulinoma. However, a routine plasma insulinoma screen-detected glimepiride. Directed history implicated a medication taken for erectile dysfunction prior to disturbed consciousness, with alcohol. The tablets, obtained online, were analysed by mass spectrometry and contained tadalafil and dapoxetine as advertised but also contained glimepiride.Learning pointsSymptomatic unexplained hypoglycaemia requires investigation with plasma glucose level, c-peptide, insulin level, pro-insulin, beta-hydroxybutyrate, and a sulphonylurea screen regardless of known exposure to sulphonylureas.Consider contamination of alternative or undisclosed medication, including PDE-5 inhibitor erectile dysfunction drugs.Concomitant alcohol may impair glycogenolysis and gluconeogenesis, exacerbating hypoglycaemia.

Absence of a sexual dimorphism in postprandial glucose metabolism after administration of a balanced mixed meal in healthy young volunteers

Background/ObjectivesA different ability to regulate glucose homeostasis between men and women may contribute to their difference in diabetes prevalence and in its predisposing conditions. Data on this issue are controversial because of heterogeneous protocols and insufficient control of confounders affecting glucose metabolism like age, body composition, and physical activity level. To clarify this issue, we compared among sexes the postprandial glucose metabolism after the administration of a balanced mixed meal normalized to daily energy expenditure.Subjects/MethodsThirty-six healthy young volunteers (18 men and 18 women; age, 23.9 ± 2.8 years; BMI, 21.9 ± 1.7 kg/m2) were recruited for the experiment. After overnight fast, subjects consumed a mixed meal providing 40% of daily energy expenditure (60% carbohydrates, 25% lipids, 15% proteins) estimated multiplying resting energy expenditure, obtained by Harris & Benedict equation, for the corresponding physical activity level. Blood was sampled at 0, 10, 20, 30, 45, 60, 90, 120, and 180 min and serum concentrations of glucose, insulin, and C-peptide were measured.ResultsFasting serum glucose concentrations were lower in women than in men, while fasting insulin and C-peptide concentrations did not differ between sexes. Linear mixed models did not show any significant effect of sex and sex # time interaction on postprandial serum glucose, insulin, and C-peptide concentrations. The comparison of areas under the curve between the sexes revealed similar glycemic, insulinemic, and C-peptide postprandial responses between men and women.ConclusionsOur results do not support the hypothesis of a sexual dimorphism in the regulation of carbohydrate metabolism in young when a mixed meal normalized on individual daily energy expenditure is ingested.

FREQUENCY OF INCREASED PLASMA C-PEPTIDE LEVELS IN COLORECTAL CANCER PATIENTS

Objective: To assess the increased frequency of serum C-peptide levels in patients of colorectal carcinoma.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Combined Military Hospital, Rawalpindi Pakistan, from Jul 2018 to Jan 2019.&#x0D; Methodology: A total of 100 cases of colorectal carcinoma were enrolled. Blood samples were obtained to assess C-peptide level. The C-peptide serum concentrations were deliberate through the Cobas 6000 by using the electro-chemi-luminescence immunoassay (ECLIA) method. If level of C-peptide was &gt;2 pmol/mL, then it was noted.&#x0D; Results: The mean age of all patients was 58.3 ± 5.4 years. There was a total of 136 (68%) females and 64 (32%) were males. The mean BMI of patients was 28.96 ± 12.31 kg/m2. The family history of colorectal carcinoma was positive in 6 (6%) cases. The mean C-peptide level was 4.55 ± 2.37 pmol/L. There were 33 (33%) patients with raised C-peptide level while 67 (67%) had normal c-peptide level.&#x0D; Conclusion: It is concluded that increased C-peptide level is high in patients with colorectal cancer.

Slow deep breathing modulates cardiac vagal activity but does not affect peripheral glucose metabolism in healthy men

Parasympathetic nervous system innervates peripheral organs including pancreas, hepatic portal system, and gastrointestinal tract. It thereby contributes to the regulation of whole-body glucose metabolism especially in the postprandial state when it promotes secretion of insulin and enhances its action in major target organs. We now aimed to evaluate the effect of parasympathetic modulation on human glucose metabolism. We used slow deep breathing maneuvers to activate the parasympathetic nervous system and tested for effects on metabolism during an oral glucose tolerance test in a randomized, controlled, cross-over trial in 15 healthy young men. We used projections towards the heart as a readout for parasympathetic activity. When analyzing heart rate variability, there was a significant increase of RMSSD (root mean square of successive differences) when participants performed slow deep breathing compared to the control condition, indicating a modulation of parasympathetic activity. However, no statistically significant effects on peripheral glucose metabolism or energy expenditure after the glucose tolerance test were detected. Of note, we detected a significant association between mean heart rate and serum insulin and C-peptide concentrations. While we did not find major effects of slow deep breathing on glucose metabolism, our correlational results suggest a link between the autonomic nervous system and insulin secretion after oral glucose intake. Future studies need to unravel involved mechanisms and develop potential novel treatment approaches for impaired insulin secretion in diabetes.

Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes

IntroductionThis study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes.Research design and methodsWe...

1192-P: Robust Arginine-Stimulated Glucagon Secretion in Patients with Type 1 Diabetes Independent of Diabetes Duration, Age, HbA1c, and Beta-Cell Secretory Capacity

In type 1 diabetes (T1D), the counterregulatory glucagon response to hypoglycemia disappears over time. It remains unknown whether this is due to lack of glucagon production or represents a malfunctioning stimulus-secretion coupling in pancreatic alpha cells. Arginine test (5 g of arginine infused intravenously (iv) over 1 minute after an overnight fast) with frequent measurements of plasma glucagon and serum C-peptide concentrations over 30 minutes was performed in 80 patients with T1D (19/61 females/males, age 49 (22-74) years (median (range)), duration 20 (2-46) years, BMI 28 (22-44) kg/m2, HbA1c 8.2 (7.5-10) %). The interrelationship between the arginine-induced glucagon response and demographic, clinical and biochemical parameters was evaluated using a stepwise approach in two multiple linear regression analysis models with glucagon area under curve (AUC) and Cmax, respectively, as dependent parameter. Mean baseline plasma glucagon concentrations amounted to 10.6±5.5 pmol/L (mean±SD). Overall, robust arginine-induced glucagon responses were observed (AUC: 499±209 pmol/L × min; Cmax: 41.0±17.7 pmol/L) independently of diabetes duration, age, HbA1c and beta cell secretory capacity. Fasting plasma glucagon and waist-to-hip ratio predicted the glucagon response in both models. When leaving out fasting plasma glucagon of the models, fasting low-density lipoprotein cholesterol and alanine aminotransferase as well as eGFR also predicted the glucagon response. In conclusion, glucagon secretory capacity in patients with T1D as assessed by iv arginine test seems preserved independently of diabetes duration, age, HbA1c and beta cell secretory capacity positioning pharmaceutical restoration of the glucagon counterregulatory response to hypoglycemia as an attractive therapeutic strategy for the protection of insulin-induced hypoglycemia. Disclosure J. Warnøe: None. T. F. Dejgaard: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Boehringer Ingelheim International GmbH, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. N. J. Johansen: Employee; Self; Novo Nordisk. A. Lund: Speaker's Bureau; Self; Novo Nordisk, Sanofi. J. I. Bagger: None. N. J. Wewer albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Regeneron Pharmaceuticals Inc., Speaker's Bureau; Self; Merck &amp; Co., Inc., Mercodia. B. Hartmann: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. H. U. Andersen: Stock/Shareholder; Self; Novo Nordisk A/S.

Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of females.

Transgender men undergoing hormone therapy are at risk for insulin resistance. However, how virilizing testosterone therapy affects serum insulin and peripheral insulin sensitivity in transgender men is unknown. This study assessed the effect of acute, virilizing testosterone on serum insulin concentrations and insulin signaling in liver, skeletal muscle, and white adipose tissue (WAT) of female pigs as a translational model for transgender men. Females received three doses of intramuscular testosterone cypionate (TEST females; 50 mg/day/pig) or corn oil (control) spaced 6 days apart starting on the day of estrus (D0). Fasting blood was collected on D0, D3, D5, D11, and D13, and females were euthanized on D13. On D13, TEST females had virilizing concentrations of serum testosterone with normal concentrations of serum estradiol. Virilizing serum testosterone concentrations (D13) were associated with decreased serum insulin and C-peptide concentrations. Blood glucose and serum glycerol concentrations were not altered by testosterone. Virilizing concentrations of testosterone downregulated AR and ESR1 in subcutaneous (sc) WAT and upregulated transcript levels of insulin-signaling pathway components in WAT and liver. At the protein level, virilizing testosterone concentrations were associated with increased PI3K 110α in liver and increased insulin receptor (INSR) and phospho(Ser256)-FOXO1 in visceral (v) WAT but decreased phospho(Ser473)-AKT in vWAT and scWAT. These results suggest that acute exposure to virilizing concentrations of testosterone suppresses circulating insulin levels and results in increased abundance of proteins in the insulin-signaling pathway in liver and altered phosphorylation of key proteins in control of insulin sensitivity in WAT.NEW & NOTEWORTHY Acute virilizing doses of testosterone administered to females suppress circulating insulin levels, upregulate components of the insulin-signaling pathway in liver, and suppress insulin signaling in white adipose tissue. These results suggest that insulin resistance in transgender men may be due to suppression of the insulin-signaling pathway and decreased insulin sensitivity in white adipose tissue.

Association of high-density lipoprotein cholesterol subfractions with insulin resistance in Nigerians with type 2 diabetes mellitus

Background: There are conflicting reports on the relationship of each of the two subfractions of high-density lipoprotein cholesterol (HDL-C) with insulin resistance in patients with type 2 diabetes mellitus (T2DM). Information on the relationship between HDL-C subfractions and insulin resistance in Nigerian patients with T2DM is not available in the literature. Aim: The aim of this article is to determine the association between subfractions of HDL-C and insulin resistance in Nigerian patients with T2DM. Materials and Methods: Patients with T2DM who were being managed by the Endocrinology, Diabetes, and Metabolism unit of the Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, South-East Nigeria were recruited for this study, whereas individuals with normal glucose tolerance (NGT) were recruited from Nnewi town. The study was carried out within a 5-month period. History was taken and physical examination was done on study participants. Fasting venous samples were collected for plasma glucose, plasma total HDL-C, plasma HDL-C phenotypes, serum C-peptide, serum creatinine, and serum alanine transferase estimation. Homeostasis Model Assessment for Insulin Resistance (HOMA2-IRC-peptide) score was determined using plasma glucose and serum C-peptide concentrations. Data were analyzed using appropriate statistical software. Results: A total of 616 participants consisting of 400 participants with T2DM and 216 participants with NGT were recruited for the study. Difference in age, sex, and blood pressure was not statistically significant between participants with T2DM and those with NGT. There were statistically significant differences in body mass index, fasting plasma glucose, C-peptide, HOMA-IR, total HDL-C, and HDL-C subfractions between subjects with T2DM and those with NGT. There was a significant negative correlation between HOMA-IR score and each of HDL2-C (rs= −0.513, P < 0.01), HDL3-C (rs= −0.471, P < 0.01), and HDL2-C/HDL3-C ratio (rs= −0.416, P < 0.01) in subjects with T2DM. Total HDL-C (odds ratio (OR)=3, P = 0.02), HDL2-C (OR=3.87, P = 0.01), and HDL3-C (OR=2.54, P = 0.02) were significant predictors of insulin resistance in individuals with T2DM after univariate and multivariate logistic regressions. Conclusion: This study showed a negative correlation between insulin resistance and each of the HDL-C subfractions in Nigerian patients with T2DM with HDL2-C having the strongest correlation with HOMA-IR score.