Biomarkers and Diagnostic Thresholds for Congenital Hyperinsulinism.

CONTEXT: Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C-peptide in the context of hypoglycemia. OBJECTIVE: We aimed to better clarify a diagnostic threshold value of C-peptide for children presenting with CHI. DESIGN: This was a retrospective case-control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C-peptide, insulin, free fatty acid (FFA) and B-hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions. PATIENTS: All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed. RESULTS: Median [C-peptide] were statistically significantly different between CHI (147) and non-CHI (72) patients, p < 0.05. The Youden Index indicated that a [C-peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non-CHI patients (p < 0.01). Median [BOHB] was 0 µmol/L in CHI patients as compared with 2378 µmol/L for non-CHI patients (p < 0.01). Median [FFA] levels were 1910 µmol/L in the non-CHI cohort, compared with 0 in the CHI cohort (p < 0.01). CONCLUSIONS: This study suggests that a C-peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C-peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis.

Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases.

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.

Relationship Between C-Peptide Levels, Clinical Features, and Serum Data in a Brazilian Type 1 Diabetes Population with Large Variations in Genomic Ancestry.

Type 1 diabetes (T1D) is a chronic disease characterized by the immune-mediated destruction of the pancreatic beta cells responsible for insulin production. The secreted insulin and C-peptide are equimolar. Due to its longer half-life, C-peptide has become a safer means of assessing the pancreatic reserve. C-peptide levels were evaluated in a population of patients with T1D, focusing on the relationship between this variable and other factors. In addition, the influence of C-peptide on metabolic control and microvascular complications was investigated. This cross-sectional study included 95 patients who had been diagnosed with T1D at least five years earlier. These patients were evaluated using a clinical demographic survey, anthropometric data, laboratory tests, and fundoscopy. This study showed that 29.5% of patients had residual insulin secretion, which correlated directly with their age at diagnosis. No statistically significant differences in metabolic control or microvascular complications were observed between the C-peptide level groups. In addition, our results indicate that ancestry does not influence the persistence of residual C-peptide function in our highly mixed population. It is recommended that future research consider incorporating new variables, such as HLA and pancreatic autoimmunity, as factors that may influence residual ß-cell function.

Random C-Peptide and Islet Antibodies at Onset Predict ß Cell Function Trajectory and Insulin Dependence in Pediatric Diabetes.

OBJECTIVE: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes. METHODS: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aß classification system ("A+": islet autoantibody positive, "ß+": random serum C-peptide ≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2 hours postprandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6 to 12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score for each participant, and compared characteristics at baseline, and clinical outcomes at V2. RESULTS: The cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black, and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aß subgroup frequencies were 46 A+ß-(63.9%), 1 A-ß-(1.4%), 4 A+ß+(5.6%), and 21 A-ß+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r = 0.36, P = .002) and V2 (r = 0.47, P < .001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis, and type 1 diabetes genetic risk score (P < .01). At V2, the 2 ß-subgroups had lower UCPCR and higher hemoglobin A1c compared with the 2 ß+ subgroups (P < .001 and P = .02, respectively). Thirty-eight percent of A-ß+ but none of the other subgroups were insulin-independent at V2 (P < .001). CONCLUSION: C-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6 to 12 months later in racially/ethnically diverse children with new-onset diabetes.

Two cases of conventional fulminant type 1 diabetes: following the depletion process of endogenous insulin secretion and literature review.

Fulminant type 1 diabetes (FT1D) is a rapidly progressive form of diabetes in which the endogenous capacity to secrete insulin is depleted. The onset is unpredictable with conventional FT1D, and a few reports have tracked C-peptide in patients with conventional FT1D pre-onset. In this report, we present two typical cases of conventional FT1D where C-peptide was monitored from the onset of precursor symptoms to the development of diabetic ketoacidosis (DKA). Furthermore, we conducted a literature review and provide a detailed description of the process of C-peptide depletion in conventional FT1D. Case 1 involved a 72-year-old woman who initially presented with fever and fatigue. Case 2 involved a 45-year-old woman with fever, abdominal pain, and acute pancreatitis. In both cases, DKA developed five days after initial symptoms. A noteworthy observation in both cases was the drastic drop in C-peptide, which was detectable at initial presentation but depleted by the time of DKA diagnosis. These cases emphasize the importance of close follow-up of plasma glucose and serum C-peptide in cases presenting with infection and pancreatitis. Our literature review revealed that in conventional FT1D, endogenous insulin secretion becomes deficient in an average of 5.3 days. Regardless of any concomitant acute pancreatitis and/or pancreas enlargement, the period until endogenous insulin secretion became deficient showed no substantial variation. This result supports the concept that progression of conventional FT1D is more rapid than that of immune checkpoint inhibitor-related FT1D, which deplete insulin secretion in approximately 2 weeks. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00755-0.

Potential of Fasting C-peptide to Glucose Ratio and Triglyceride Glucose Index as Markers for ß-Cell Dysfunction and Insulin Resistance in Patients With Type 2 Diabetes on Insulin Therapy.

BACKGROUND: Pathogenesis of type 2 diabetes mellitus (T2DM) is combined from initial insulin resistance (IR) and subsequent ß-cell dysfunction. Insulin therapy can replace ß-cell function in advanced stages. However excessive insulin therapy increases IR and may expose the patients to risk of cardiovascular disease. We aim to assess ß-cell function and IR in patients with type 2 diabetes on insulin therapy by fasting C-peptide to glucose ratio (FCPGR), and triglyceride glucose (TyG) index respectively to support treatment plans. METHOD: A cross-sectional study was conducted at the Galiawa Diabetes and Endocrinology Teaching Center in Erbil City, Iraq, from June 2023 to January 2024. A convenient sample of 100 patients with T2DM on insulin-based therapy were included after obtaining informed written consent and excluding conditions such as acute illness, uncertain type of diabetes, etc. Each patient was evaluated for anthropometric parameters and current treatment details. Biochemical tests were then carried out to calculate metabolic syndrome (MetS) index score, FCPGR, and TyG index. Finally, patients were divided into four subgroups according to their FCPGR and TyG index and the data were analyzed statistically. RESULT: The data showed those patients with sufficient ß-cell function were 60 (60%), and patients with high TyG index were 95 (95%). There was a significant negative correlation between FCPGR and hemoglobin A1c (HbA1c) (p-value=0.001), while there was a positive correlation between TyG index and HbA1C (p-value=0.001). None of these markers were correlated with BMI (p-value=0.297, and 0.976), duration of T2DM (p-value=0.258, and 0.458), and dose of insulin therapy (p-value=0.901, and 0.477). Patients with sufficient ß-cell function and high TyG index had the lowest HbA1C. CONCLUSION: The study provides valuable insights into the utility of FCPGR and TyG index as biomarkers for ß-cell function and insulin resistance in T2DM patients on insulin therapy. The significant correlation with HbA1C underscores their potential in clinical practice. However, the lack of correlation with BMI, disease duration, and insulin dose suggests that further investigation is needed to fully understand these biomarkers' implications across diverse patient profiles.

Clinical Utility of Serum C-Peptide Concentration for Hospitalized Patients with Hyperglycemia.

Background: Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there are limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Materials and Methods: Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study. Predictive capacity of C-peptide for discontinuation of therapeutic insulin was examined in the entire cohort and the subgroup of non-autoimmune non-pancreatitis diabetes (NANP-DM). Results: We included 187 patients (63 women) in our study. During hospitalization, patients with type 1 diabetes antibodies displayed diminished serum C-peptide concentration (P = 0.014), correlating inversely with subsequent hemoglobin A1c% [r = (-0.22), P = 0.005]. Initial C-peptide concentrations did not differ between patients requiring insulin therapy during follow-up and those who did not (P = 0.16). C-peptide concentrations showed limited predictive capacity for achieving glycemic control. Subgroup analyses in NANP-DM exhibited similar limited capacity for anticipating therapeutic insulin needs and achieving glycemic controls. Discussion: C-peptide concentration did not exhibit a robust predictive capability for future need of insulin therapy and achieving glycemic control, limiting its utility in clinical practice within inpatient settings.

The Predictive Potential of C-Peptide in Differentiating Type 1 Diabetes From Type 2 Diabetes in an Outpatient Population in Abu Dhabi.

PURPOSE: We aimed to investigate the predictive potential of plasma connecting peptide (C-peptide) in differentiating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based diabetes classification criteria. METHODS: A retrospective review was performed of all the patients with diabetes visiting an outpatient diabetology, endocrinology, general practice and family medicine tertiary health care center between January 2016 and December 2021. FINDINGS: Two hundred twelve individuals with diabetes were included, 85 (44.8%) with T1D and 127 (55.2%) with T2D. Mean (SD) age at diagnosis was 35.9 (15.1) years, and 112 (52.8%) men. Median (interquartile range [IQR]) duration of diabetes was 3.8 (3.0-4.5) years (T1D, 3.9 [3.5-4.6]; T2D, 3.4 [2.4-4.4]; P = 0.001). Body mass index was <18.5 kg/m2 in 5 (2.5%) individuals (T1D, 5; T2D, none), 18.5 to <25 kg/m2 in 57 (28.5%) (T1D, 32; T2D, 25), 25 to <30 kg/m2 in 58 (29%) (T1D, 28; T2D, 30), and >30 kg/m2 in 80 (40.0%) (T1D, 20; T2D, 60). Median (IQR) glycosylated hemoglobin was 7.4% (6.7%-8.5%) (T1D, 8.3% [7.2%-9.9%]; T2D, 7% [6.3%-7.6%]; P = 0.0001). Median (IQR) C-peptide concentration was 0.59 nmol/L (0.01-1.14 nmol/L) (T1D, 0.01 nmol/L [0.003-0.05 nmol/L]; T2D, 1.03 nmol/L [0.70-1.44 nmol/L]; P = 0.0001). C-peptide concentration of ≤0.16 nmol/L showed 92.9% sensitivity, 1-specificity of 2.4%, and AUC of 97.2% (CI, 94.7%-99.6%; P = 0.0001) in differentiating T1D from T2D. IMPLICATIONS: To our knowledge, this is the first study in the Middle East and North Africa region highlighting the role of C-peptide in diabetes classification. The estimated cutoff point for C-peptide concentration (≤0.16 nmol/L) will certainly help in accurately classifying the T1D and will rule out the routine clinical judgmental approaches in the region, especially in those scenarios and periods where it is always difficult to diagnose the diabetes type. Quantifying the cutoff for C-peptide is among the vital strengths of this study that will provide a better treatment plan in diabetes care management. Also, we evaluated concomitant glucose levels to rule out the phenomenon of falsely low C-peptide values in the setting of hypoglycemia or severe glucose toxicity. Based on our findings, C-peptide testing could be included in postulating an evidence-based guideline that differentiates T1D from T2D. Despite this, our study has some limitations, including the selection bias due to the retrospective design and low C-peptide levels could be indicative of low pancreatic reserves due to other causes or long-standing T2D, and quantifying these reasons requires additional resources and time.

Evaluation of teplizumab's efficacy and safety in treatment of type 1 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus (T1DM). Teplizumab, a humanized anti-CD3 monoclonal antibody, may help T1DM. Its long-term implications on clinical T1DM development, safety, and efficacy are unknown. AIM: To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM. METHODS: A systematic search was conducted using four electronic databases (PubMed, Embase, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) were calculated, along with their 95%CI. We assessed heterogeneity using Cochrane Q and I 2 statistics and the appropriate P value. RESULTS: There were 8 randomized controlled trials (RCTs) in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts, with 1361 patients receiving Teplizumab and 547 patients receiving a placebo. Teplizumab was found to have a substantial link with a decrease in insulin consumption, with an OR of 4.13 (95%CI: 1.72 to 9.90). Teplizumab is associated with an improved C-peptide response (OR 2.49; 95%CI: 1.62 to 3.81) and a significant change in Glycated haemoglobin A1c (HbA1c) levels in people with type 1 diabetes [OR 1.75 (95%CI: 1.03 to 2.98)], and it has a RR of 0.71 (95%CI: 0.53 to 0.95). CONCLUSION: In type 1 diabetics, teplizumab decreased insulin consumption, improved C-peptide response, and significantly changed HbA1c levels with negligible side effects. Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.

Pseudo-nephropathy and hyper-excretion of urinary C-peptide: an overlooked adverse effect of an angiotensin receptor-neprilysin inhibitor (ARNI).

Sacubitril/valsartan, which is a combined angiotensin receptor-neprilysin inhibitor (ARNI), is used for the treatment of chronic heart failure and hypertension. Substrates of neprilysin are numerous, and the systemic effects of an ARNI remain to be determined. Increased urinary C-peptide (UCPR) and urinary albumin (UAlb) excretion has been reported with the use of an ARNI, but the mechanism is still unknown. We report an 84-year-old man with type 2 diabetes and hypertension. His UAlb and UCPR excretion and (to a lesser degree) the estimated glomerular filtration rate were increased after ARNI administration. They returned to basal levels after discontinuing ARNI administration. There was little or no change in glycemic control. Therefore, increased glomerular permeability and filtration could partially explain how neprilysin inhibition led to an elevation in UCPR excretion, in addition to other mechanisms, such as impairment of the renal ability to degrade C-peptide. Physicians must be cautious when interpreting the insulin secretion capability by UCPR and nephropathy by UAlb in ARNI-treated patients with diabetes.

Obesity as a misleading factor in the diagnosis of type 1 diabetes mellitus: A case report.

A comprehensive evaluation, including symptoms, medical history, C-peptide levels, and anti-GAD antibodies, is essential for distinguishing between diabetes' types, particularly in cases of diagnostic uncertainty. While obesity is often associated with T2DM, BMI should be viewed as a factor rather than a criterion for the exclusion of diabetes type.

New Onset Diabetes After COVID 19 (NODAC) is predominantly due to exacerbated Insulin Resistance (IR) rather than beta cell dysfunction: Lessons from tertiary care hospital data during confluence of two epidemics.

PURPOSE: To investigate determinants of new onset diabetes after COVID-19 (NODAC) and its recovery at 6 months. METHODS: This was an observational follow up study conducted from August, 2020 to July, 2023, recruiting patients with preexisting DM and COVID 19 patients with no history of DM. Multivariate regression analysis was used to determine the factors responsible for severity of COVID 19 infection in preexisting DM group. Clinical, laboratory and glycometabolic parameters were estimated at baseline and 6 months in NODAC and euglycemic group to determine the factors responsible for NODAC and its persistence at 6 months. RESULTS: Of 1310 patients, 855 (65.3%) COVID 19 patients were further divided based on their glycemic status: preexisting DM (19%), NODAC (8.5%) and euglycemia (72.5%). Older age and male gender were independent risk factors for severe COVID 19 disease in patients with preexisting diabetes. Prevalence of NODAC in present study was 8.5%. Patients with NODAC had higher mean fasting blood glucose (FBG), random blood glucose (RBG) and HbA1c at baseline as compared to COVID with euglycemic group with no difference in serum C-peptide levels. Female gender, family history of DM, signs of insulin resistance, higher BMI, WHR, HbA1c, serum insulin levels, FBG and RBG predicted persistence of NODAC at 6 months. CONCLUSION: Preexisting DM is a risk factor for severe COVID 19 disease. Patients with NODAC have evidence of persistence insulin resistance on follow up, underscoring the need for long term glycemic monitoring.

A Case Report: Hypoglycaemic Unawareness Associated With Insulinoma.

Hypoglycaemic unawareness (HU) is more frequently described in relation to diabetics in the literature. We have noted that there is also an increasing reporting of HU in insulinoma cases. We report a hospital presentation for an incidental finding of hypoglycaemic unawareness in a gentleman in his fifties who was eventually diagnosed with insulinoma following biochemical studies, radiologic evaluation and histologic evaluation of an excised lesion between the pancreas and the spleen. We have reviewed existing literature evidence regarding the possible aetiologies and management options for this occurrence. More research studies to identify the epidemiology of this association and the determination of a protocol for increased detection of patients with insulinoma who display HU will need to be done.

Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of ß-cell function.

OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.

Development and Validation of a Novel Isotope Dilution-Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Method for Serum C-Peptide.

Background: Mass spectrometry (MS) methods exhibit higher accuracy and comparability in measuring serum C-peptide concentrations than immunoassays. We developed and validated a novel isotope dilution-ultraperformance liquid chromatography-tandem MS (ID-UPLC-MS/MS) assay to measure serum C-peptide concentrations. Methods: Sample pretreatment involved solid-phase extraction, ion-exchange solid-phase extraction, and derivatization with 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (Cayman Chemical, Ann Arbor, Michigan, USA). We used an ExionLC UPLC system (Sciex, Framingham, MA, USA) and a Sciex Triple Quad 6500+ MS/MS system (Sciex) for electrospray ionization in positive-ion mode with multiple charge states of [M+3H]3+ and multiple reaction monitoring transitions. The total run time was 50 mins, and the flow rate was 0.20 mL/min. We evaluated the precision, trueness, linearity, lower limit of quantitation (LLOQ), carryover, and matrix effects. Method comparison with electrochemiluminescence immunoassay (ECLIA) was performed in 138 clinical specimens. Results: The intra- and inter-run precision coefficients of variation were <5% and the bias values for trueness were <4%, which were all acceptable. The verified linear interval was 0.050-15 ng/mL, and the LLOQ was 0.050 ng/mL. No significant carryover or matrix effects were observed. The correlation between this ID-UPLC-MS/MS method and ECLIA was good (R=0.995, slope=1.564); however, the ECLIA showed a positive bias (51.8%). Conclusions: The developed ID-UPLC-MS/MS assay shows acceptable performance in measuring serum C-peptide concentrations. This will be useful in situations requiring accurate measurement of serum C-peptide in clinical laboratories.

Abnormal late postprandial glucagon response in type 1 diabetes is a function of differences in stimulated C-peptide concentrations.

Background: The functional changes in alpha cells in patients with type 1 diabetes (T1D) with different residual beta cell functions remain poorly elucidated. The study aimed to investigate the relationship between glucagon secretion and C-peptide levels and to explore the relationship between glucagon response and glucose increment in respond to a secretagogue in a steamed bread meal tolerance test (BMTT) in T1D. Methods: The study enrolled 43 adult patients with T1D and 24 healthy control subjects. Patients with T1D who underwent BMTT were divided into two groups based on peak C-peptide levels: C peptide low (CPL; C-peptide < 200 pmol/L; n=14) and high (CPH; C peptide ≥ 200 pmol/L; n=29). Plasma glucose, C-peptide, glucagon levels at 0, 30, 60, 120, and 180 min were measured. The glucagon response to the BMTT was defined by areas under the curve (AUC) as early (AUC0-30), late (AUC30-180), or total (AUC0-180) glucagon. Results: Compared to healthy individuals, fasting plasma glucagon was lower and postprandial plasma glucagon level was increased in patients with T1D. Glucagon levels after BMTT between the CPL and CPH group showed significant group by time interaction. Peak glucagon and glucagon at 60-180 min, total and late glucagon response were higher in CPL than CPH group, while fasting glucagon and early glucagon response adjusted for glucose were comparable between CPL and CPH group. The higher late glucagon response and late glucagon response adjusted for glucose were associated with lower peak C-peptide in T1D. The higher late glucagon response and lower peak C-peptide were associated with the higher value of ▵glucose at 180 min. Conclusion: Stimulated C-peptide levels affect the paradoxical increase in postprandial glucagon secretion in patients with T1D, especially late glucagon response. The exaggerated postprandial glucagon secretion further stimulates the elevation of postprandial glucose in patients with T1D.

C-peptide: an essential ally in microvascular complications of type 2 diabetes mellitus and obesity.

BACKGROUND: In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. METHODS: Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. RESULTS: Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05). CONCLUSIONS: Establishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.