Serum C-peptide Research Articles

Serum C-peptide level and the risk of cardiovascular diseases mortality and all-cause mortality: a meta-analysis and systematic review.

Recently, the serum of C-peptide has been the focus of researchers as a possible predictor of mortality. However, the possible association of serum C-peptide with cardiovascular diseases (CVDs) mortality and all-cause mortality has not been clearly identified. This meta-analysis aimed to assess the relationship between serum C-peptide and the risk of CVDs mortality and all-cause mortality. A comprehensive and systematic search was performed in various important databases, including the PubMed, Web of Science, and Scopus to find relevant studies up to November 2022. The reported hazard ratio (HR) [95% confidence interval (CI)] for all studies was converted into log HR, and their SD was calculated. Then to compute the pooled HR, the random-effects model with inverse variance weighting method was performed. Twenty-three studies were included in the meta-analysis. Fourteen studies reported HR for all-cause mortality, and nine studies for CVDs-related mortality. The pooled results indicate a significant association between serum C-peptide and the risk of all-cause mortality (HR: 1.22; 95% CI: 1.12-1.32, I2 = 76.8%; P-value < 0.001). Also, higher serum C-peptide was related to the increased risk of CVDs mortality (HR: 1.38; 95% CI: 1.08-1.77, I2 = 81.8%; P-value = 0.012). Our investigation suggested that an increased level of serum C-peptide is associated with a higher risk of both CVDs and all-cause mortality. Further, large-scale studies and sufficient samples are recommended to present a convincing link between C-peptide and the risk of CVDs and all-cause mortality. identifier, CRD42022364842.

Insulin autoimmune syndrome

Insulin autoimmune syndrome (IAS), also known as Hirata's disease, is a rare endocrine disease. It is a form of autoimmune endogenous hyperinsulinemic hypoglycemia, which develops when genetically predisposed individuals get exposed to triggering factors such as viral infection or certain medications containing sulfhydryl groups. It is important to consider IAS in the differential diagnosis of hypoglycemia as its incidence seems to be increasing worldwide. In this article, we summarize a report of two cases of IAS and their clinical manifestations, biochemical characteristics, their step-by-step diagnosis, and also prompt utilization of continuous glucose monitoring system as a monitoring tool for appropriate management. The first patient who presented with hypoglycemic episodes had recently suffered from a viral pneumonia, which probably acted as a superantigen and triggered development of IAS. The second patient also had hypoglycemic episodes, which used to recover after intake of glucose-containing liquids. Alpha-lipoic acid containing multivitamin may have triggered the development of IAS in the second patient. The tests performed showed high serum insulin and C-peptide levels along with insulin autoantibody positivity confirming the diagnosis of Hirata's disease. Immunosuppression therapy was not required as both the patients responded well to diet modification and corticosteroid therapy. It is important to be mindful while prescribing alpha-lipoic acid-containing supplements though it has good antioxidant properties, as it is presumed to be associated with increasing number of IAS cases.

Non-islet cell tumour hypoglycaemia: A rare cause of persistent hypoglycaemia.

Non-islet cell tumour hypoglycaemia (NICTH) is a rare cause of hypoglycaemia. There is no single pathogenic mechanism that can explain all cases of NITCH. With this case, we wish to highlight the complexity in diagnosis and management of this condition.

Effects of High-Intensity Interval Training on Melatonin Function and Cellular Lymphocyte Apoptosis in Sedentary Middle-Aged Men.

Background: Physical performance increased by controlled interventions of high-intensity intermittent training (HIIT); however, little is known about their influence as anti-aging and antioxidant effects, or their role in mitochondrial biogenesis. Purpose: This study aimed to determine the effects of HIIT for 12 weeks on melatonin function, lymphocyte cell apoptosis, oxidative stress on aging, and physical performance. Methods: Eighty healthy male subjects aged 18-65 years randomly participated in a HIIT-exercise training program for 12 weeks. Anthropometric analysis, cardiovascular fitness, total antioxidant capacity (TAC), lymphocyte count and apoptosis, and serum melatonin and cytochrome c oxidase (COX), were estimated for all subjects before and after HIIT-exercise training. HIIT training was performed in subjects for 12 weeks. Results: Data analysis showed a significant increase in the expression levels of the melatonin hormone (11.2 ± 2.3, p < 0.001), TAC (48.7 ± 7.1, p < 0.002), COX (3.7 ± 0.75, p < 0.001), and a higher percentage of lymphocyte apoptosis (5.2 ± 0.31, p < 0.003). In addition, there was an improvement in fitness scores (W; 196.5 ± 4.6, VO2max; 58.9 ± 2.5, p < 0.001), adiposity markers (p < 0.001); BMI, WHtR, and glycemic control parameters (p < 0.01); FG, HbA1c (%), FI, and serum C-peptide were significantly improved following HIIT intervention. Both melatonin and lymphocyte apoptosis significantly correlated with the studied parameters, especially TAC and COX. Furthermore, the correlation of lymphocyte apoptosis with longer exercise duration was significantly associated with increased serum melatonin following exercise training. This association supports the mechanistic role of melatonin in promoting lymphocyte apoptosis either via the extrinsic mediator pathway or via inhibition of lymphocyte division in the thymus and lymph nodes. Additionally, the correlation between melatonin, lymphocyte apoptosis, TAC, and COX activities significantly supports their role in enhancing physical performance. Conclusions: The main findings of this study were that HIIT exercise training for 12 weeks significantly improved adiposity markers, glycemic control parameters, and physical performance of sedentary older adult men. In addition, melatonin secretion, % of lymphocyte apoptosis, COX activities, and TAC as biological aging markers were significantly increased following HIIT exercise training interventions for 12 weeks. The use of HIIT exercise was effective in improving biological aging, which is adequate for supporting chronological age, especially regarding aging problems. However, subsequent studies are required with long-term follow-up to consider HIIT as a modulator for several cardiometabolic health problems in older individuals with obesity.

Pregnancy induces longitudinal changes in Urinary C-peptide Creatinine Ratio in women with type 1 diabetes.

Changes in maternal serum C-peptide have been described during pregnancy in women with Type 1 diabetes. We aimed to determine whether in these women, C-peptide, as measured by the urinary C-peptide creatinine ratio (UCPCR), display changes during the course of pregnancy and in the postpartum period. In this longitudinal study including 26 women, UCPCR was measured in the first, second and third trimester of pregnancy, and postpartum, using a high sensitivity two-step chemiluminescent microparticle immunoassay. UCPCR was detectable in 7/26 (26.9%) participants in the first trimester, 10/26 (38.4%) in the second trimester, 18/26 (69.2%) in the third trimester. Changes in UCPCR concentrations were observed throughout pregnancy, significantly increasing from first to third trimester. UCPCR concentration in the three trimesters was associated with a shorter duration of diabetes, and, in the third trimester also with first trimester UCPCR. UCPCR detects longitudinal changes during pregnancy in women with type 1 diabetes mellitus, more marked in those with shorter diabetes duration.

839-P: Alpha-1 Antitrypsin Augmentation Therapy in Chronic Pancreatitis Patients Undergoing Total Pancreatectomy and Islet Autotransplantation

Stress-induced islet graft loss reduces the efficacy of islet transplants. In this single-center, randomized, double-blind, and controlled clinical trial, we evaluated the safety and efficacy of human alpha-1 antitrypsin (AAT) infusion in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT) at the Medical University of South Carolina. Among 48 qualified subjects randomized in a 1:2 (placebo vs AAT) ratio, 43 received TP-IAT. Subjects were given saline or AAT infusion at 60mg/kg weekly for 4 weeks and were followed for 12 months. The primary efficacy endpoint was the islet function measured by the C-peptide area under the curve during a mixed meal tolerance test (MMTT) at Month 12 (M12). Adverse events (AEs) were measured throughout the study. Safety, glycemic control, insulin use, and quality of life (QoL) were compared between groups. Safety evaluation showed no significant differences in the types and severity of participant AEs. The primary efficacy outcome was not significantly different between groups. Baseline characteristics including age, body weight, BMI, HbA1C, etc, were comparable in the randomized populations. The oxygen consumption rate before the transplant was higher in the AAT group. Serum C-peptide (an indicator of islet death) was lower in the AAT group, suggesting less islet injury. AAT subjects trended toward better SF-12 physical QoL and lower insulin use at both 75 and 365 days post-IAT. Despite intensive efforts to get participants to return for the Day 365 MMTT, only 10/14 (71%) in the placebo group and 18/29 (62%) in the AAT group returned for this test. Although we did not observe a statistical difference in islet function using AAT therapy, we gained a better understanding of this patient population. Minimizing numbers of follow-up visits, use of fewer doses of medication with higher doses, and providing travel are all important for future clinical trials in TP-IAT. Disclosure H. Wang: None. W. Gou: None. D. Adams: None. K. Morgan: Speaker's Bureau; Johnson &amp; Johnson Medical Devices Companies. P.J. Nietert: None. J. Hirsch: None. C. Strange: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK105183, DK120394, DK118529); U.S. Department of Veterans Affairs (I01BX004536 to H.W.)

241-OR: Preservation of Islet Graft Function and Blood Glucose Control after Total Pancreatectomy with Islet Autotransplantation in Patients with Chronic Pancreatitis and Intractable Pain—Nine-Year Follow-up

Background: Total pancreatectomy is a last resort treatment for patients with chronic pancreatitis and intractable abdominal pain, however its utility has been hampered by the uncertain endocrine outcomes of islet transplantation and risk of postsurgical diabetes. Here, we present our 9-year clinical results after total pancreatectomy and islet transplantation. Materials and Method: Forty-one patients with chronic or recurrent acute pancreatitis were treated with TPIAT over the last 9 years at the University of Chicago Medical Center. There were 15 male and 26 female with a median age of 33 (6-65) and with median BMI of 25 (17-39). Five (12%) patients were already diabetic prior to surgery. Islet isolation was performed at a local laboratory compliant with current Good Manufacture Practice regulations. Islet purification was implemented in 4 (10%) cases to reduce islet pellet volume below 20mL for intraportal infusion. Results: All patients required opioids for pain control prior to surgery. Most of the patients (93%) reported resolution of pancreatic-type pain by postoperative year one. The number of patients requiring opioids for different type or location of pain declined over time from 13 (31%) at 1 year to 5 (12%) at 5 years after TPIAT. During TPIAT patients received on average 211,000±111,000 islet equivalents (IEQ), 2,500±1,600,). The majority of patients (95%) maintained endocrine beta cell function during follow up (serum c-peptide &amp;gt;0.5ng/ml). Over 40% of patients maintained long-term insulin independence: 44% (15/34) at 1-year and 45% (5/11) at 5-year follow-up. Conclusions: TPIAT successfully provided pancreatic pain resolution of pancreatic pain and preservation of the endocrine beta cell function in majority of the patients with no mortality. Islet autotransplantation prevented diabetes in over 40% of patients. Disclosure W.Lin: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.Ogledzinski: None. S.Gondek: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020595)

1493-P: Immune-Mediated Diabetes Mellitus—A Rare Complication of Nivolumab Therapy

Background: Immune mediated diabetes mellitus (DM) is a rare complication of immune checkpoint inhibitor (ICI) therapy, with an incidence of less than 1%. We present a case of immune-mediated DM with nivolumab therapy presenting as diabetic ketoacidosis (DKA). Case: A 74-year-old Caucasian male with no history of DM or autoimmune disease was diagnosed with stage III metastatic melanoma and started on treatment with nivolumab, an ICI. He tolerated treatment well and had no evidence of endocrine dysfunction on routine laboratory monitoring. Shortly after completing his 14th cycle of nivolumab therapy, he presented to the emergency department with a one-week history of fatigue, poor appetite, polydipsia, and polyuria. He was found to have DKA with serum blood glucose 446 mg/dL, anion gap 20 mEq/L, serum bicarbonate 14 mEq/L, arterial pH 7.23, and 4+ urine ketones. His hemoglobin A1c was 7.3%, increased from 5.4% one year earlier. He was treated with intravenous insulin then transitioned to basal-bolus subcutaneous insulin therapy, which was continued at discharge. Evaluation in the outpatient setting revealed no measurable GAD65 antibodies or anti-insulin antibodies, but his serum c-peptide was found to be &amp;lt;0.10 ng/mL with corresponding serum blood glucose level 214 mg/dl. This supported a diagnosis of endocrine pancreatic insufficiency, in his case likely immune mediated due to nivolumab therapy. He completed an additional 6 cycles of nivolumab with no further complications. Meanwhile his DM became well-controlled with subcutaneous insulin injections, and he was eventually transitioned to insulin pump therapy. Discussion: ICIs such as nivolumab are known to cause multiple autoimmune complications that can appear at any point during treatment. The underlying mechanisms of beta cell immunotoxicity are incompletely understood, but progression to insulin-dependency appears to be rapid. It is important to recognize new or worsening DM early to avoid life-threatening complications such as DKA. Disclosure S.M.Iqbal: None. C.Houston: None.

1425-P: C-Peptide and Islet Autoantibodies at Diagnosis Predict Long-Term ß-Cell Function and Insulin Dependence in Pediatric Diabetes

We asked if assessment of islet autoimmunity and β cell function in children at diabetes diagnosis is useful for prognosis, using the “Aβ” system, [“A” representing autoimmunity (A+ = ≥1 autoantibody; A- = no antibodies), “β” representing β cell function (β+ = random serum C-peptide ≥0.6 ng/mL; β- = C-peptide &amp;lt;0.6 ng/mL)]. We followed β cell function longitudinally with 2h post-prandial urinary C-peptide-creatinine ratio (UCPCR) at 3-12 wk (V1) and 6-12 m (V2). We compared clinical characteristics, glycemia and β cell function at baseline and clinical outcomes at V2 between the groups. The cohort (n=74) was 50% female, 76% White, 22% non-Hispanic Black, 2% Other, 47% Hispanic. Median age (25p-75p) was 12.6 (8.5-14.6) years, median BMI 70.7 (16.7-96.1) %ile. Phenotypic frequencies were A+β- (36.5%), A-β+ (29.7%), A+β+ (31.1%) and A-β- (2.7%). Baseline serum C-peptide correlated with UCPCR at V1 (r=0.37, p=0.03). Adjusting for age, sex, race/ethnicity, and BMI, UCPCR at V2 was higher in A-β+ than A+β- (β=1.18, 95% CI:0.31-2.07, p=0.009). Fully 36% of A-β+ but none of A+β+ and A+β- were insulin-independent at V2 (p&amp;lt;0.001). The remaining results are shown in Table 1. The A-β+ phenotype at diagnosis predicts sustained β cell function and potential insulin-independence after 6-12 months. Random serum C-peptide at diagnosis correlates with 2h post-prandial UCPCR at 3-12 weeks. Disclosure M.Tosur: Advisory Panel; Provention Bio, Inc. A.Balasubramanyam: None. X.C.Huang: None. S.Deen: None. S.Uysal: None. M.Astudillo: None. W.Hagopian: Research Support; Janssen Research &amp; Development, LLC, Provention Bio, Inc., Randox R &amp; D. R.A.Oram: Consultant; Janssen Research &amp; Development, LLC, Research Support; Randox R &amp; D. F.Jahoor: None. M.J.Redondo: None. Funding Texas Children's Hospital (to M.T.); Rutherford Fund (to A.B.); National Institutes of Health (K23DK129821 to M.T.)

240-OR: Islet Allotransplantation into Prevascularized Sernova Cell Pouch—Early Results from the University of Chicago

Each of 6 patients with T1DM and problematic hypoglycemia received 2 islet transplants into pre-implanted Sernova Cell Pouches (SCPs). Each procedure involved transplantation of islets into two 8-channel SCPs and one mini sentinel SCP. SCP implants and the combination of SCP with human cadaveric islets are both well tolerated with durations exceeding 3 years. Detectable islet function (≥0.3ng/ml peak serum c-peptide in mixed meal tolerance test) was achieved in 4 patients following islet transplant to SCP. It was correlated with transplanted islet mass of 300k-500k IEQ per procedure. Transplantation of islet mass &amp;lt;300k IEQ did not lead to detectable c-peptide secretion. C-peptide was detectable for periods ranging from days up to 12 months after the procedure. Three patients with suboptimal levels of immunosuppression due to non-compliance experienced antibody mediated rejection based on de novo donor specific antibodies (DSAs). One patient with DSAs had detectable stimulated c-peptide at 90 days post-transplant. Histological assessment of sentinel SCPs retrieved ≥90 days post-transplant revealed surviving functional islets within vascularized SCP channels via positive immunofluorescence staining of insulin, c-peptide, glucagon and somatostatin in 5 of 6 patients. Five patients received supplemental intraportal islet transplants (IPITx) and all of them remain insulin independent (&amp;gt;2.5Y, &amp;gt;1Y, 10M, 2M, 1M). The sixth patient is awaiting an IPITx in the coming months as per protocol. Safety and dose-response observations from the first cohort of 6 patients led to the implementation of 10-channel SCPs with 50% greater transplant capacity than the 8-channel configuration in a second study cohort. Two additional patients were recently implanted with 10-channel SCPs and are currently awaiting their first islet transplantation. Disclosure M.Ogledzinski: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. S.Gondek: None. W.Lin: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None. Funding Sernova; JDRF

184-LB: The Effect of Early Screening and Intervention for Gestational Diabetes Mellitus on Pregnancy Outcomes—The TESGO Randomized Controlled Trial

Background: Women with gestational diabetes mellitus (GDM) have excessive fetus growth weeks earlier than the recommended screening period, suggesting that earlier screening and intervention may improve pregnancy outcomes and the health of the offspring. This trial aimed to investigate if early screening and intervention could alter pregnancy outcomes, compared to the standard group. Methods: We conducted an open-label randomized controlled trial in singleton pregnant women at National Taiwan University Hospital from 2018 to 2021. GDM is diagnosed by 75g 2-hour oral glucose tolerance tests at 18-20 weeks of gestational age for the early-screening group and at 24-28 weeks for the standard-screening group. The diagnostic cutoffs are according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. The primary outcome is a composite measure of pregnancy outcomes, including primary cesarean section, birth weight &amp;gt;90th percentile, neonatal hypoglycemia, cord serum C-peptide &amp;gt;90th percentile, gestational hypertension, preeclampsia and birth trauma. Results: Total 967 subjects were enrolled, including 483 subjects in the early-screening group and 484 subjects in the standard-screening group. Primary outcome was not statistically different between the two groups (early-screening group, 34.74%; standard-screening group 30.75%, p=0.20). There was also no significant difference in each individual outcome of the primary outcome between two groups except neonatal hypoglycemia, which was significantly higher in the standard-screening group than in the early-screening group (4.14% vs. 1.71%, p=0.0278). Conclusions: Early screening and intervention of GDM by the one-step method does not improve pregnancy outcomes as compared to standard practice. Disclosure C. Kuo: None. S. Lin: None. M. Lin: None. C. Lee: None. C. Chang: None. Y. Chang: None. Y. Tai: None. S. Chen: None. I. Yen: None. K. Fan: None. C. Hsu: None. K. Huang: None. W. Hsu: None. J. Kang: None. H. Li: None.

1463-P: Heterozygous Variant in NFKB1 Presenting with Autoantibody-Negative (AbNeg) Insulin-Dependent Diabetes (IDDM)

Due to its uncertain etiology and clinical management, AbNeg IDDM is a phenotype of interest for the NIH-funded Rare and Atypical Diabetes Network (RADIANT), which aims to identify and characterize people with unknown forms of diabetes (DM). We report a case of childhood-onset AbNeg IDDM found to have a likely pathogenic variant in NFKB1. A 17-year-old female presented with DM at age 7 with A1c 10.8%; random C-peptide 0.21 ng/ml; no diabetic ketoacidosis; negative GAD65, insulin, IA-2 and ZnT8 Ab; normal BMI%ile; no signs of insulin resistance; and negative genetic testing for monogenic DM. She has required continuous insulin therapy. Past medical history: IgA deficiency, vitamin D deficiency, orthostatic intolerance, neurocardiogenic pre-syncope and chronic migraine. Family history: Autoimmune adult-onset DM and hypothyroidism in mother, frequent upper respiratory infections in sisters, Addison’s disease in maternal grandfather, hemochromatosis in paternal grandmother and pericarditis at age 30 in paternal grandfather. Physical exam: Unremarkable. RADIANT Labs: Undetectable serum C-peptide. Negative Ab. Whole genome sequencing: Heterozygous likely pathogenic variant in NFKB1 impacting the canonical splice acceptor sequence (NM_003998.4:c.1753-1G&amp;gt;C). This is a case of youth-onset AbNeg IDDM found to have a likely pathogenic variant in NFKB1. Heterozygous loss-of-function variants in NFKB1 are associated with Common Variable Immunodeficiency (CVID) type 12 (OMIM #616576), characterized by incomplete penetrance and variable expressivity of immunodeficiency and autoimmunity, including features of IDDM. Immune dysregulation may explain lack of classic Ab. There are no prior reports of CVID first ascertained through a DM phenotype. Thus, this case represents a phenotype expansion of NFKB1-associated disease, and contributes to our understanding of the heterogeneity of AbNeg IDDM. Genetic testing of first-degree relatives is underway. Disclosure M.J.Redondo: None. A.Balasubramanyam: None. P.Liu: Other Relationship; Baylor Genetics. A.N.Alkanaq: None. M.Tosur: Advisory Panel; Provention Bio, Inc. N.Ram: None. R.J.Kreienkamp: None. E.A.Oral: Advisory Panel; Amryt Pharma Plc, Regeneron, Rejuvenate Bio, Third Rock Ventures, Consultant; Amryt Pharma Plc, Ionis Pharmaceuticals, Regeneron, Other Relationship; Amryt Pharma Plc, Research Support; Amryt Pharma Plc, Novo Nordisk, Fractyl Health, Inc., Ionis Pharmaceuticals, Regeneron, GI Dynamics, Rejuvenate Bio. C.Pihoker: None. J.Posey: None. Funding National Institutes of Health (U54DK118638)

Development of Fulminant Type 1 Diabetes Mellitus in the Course of Treatment with Atezolizumab for Hepatocellular Carcinoma.

A 71-year-old woman with recurring stage IV hepatocellular carcinoma (HCC) was admitted to our hospital while being treated with atezolizumab and bevacizumab and complained of fatigue, vomiting, and appetite loss. The following were noted on admission: serum glucose level, 633 mg/dL; metabolic acidemia (HCO3- of 19.5 mmol/L); remarkably low serum and urinary C-peptide levels (0.16 ng/mL and ≤1.5 μg/day, respectively); and urinary ketone body level, 4,197 μmol/L. She was diagnosed with atezolizumab-induced fulminant type 1 diabetes mellitus (T1DM), and insulin therapy improved the symptoms. To our knowledge, this a novel report of atezolizumab-induced fulminant T1DM in an HCC patient.

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.

Obesity is associated with impaired postprandial pancreatic polypeptide secretion.

This study aims to compare the levels of serum pancreatic polypeptide (PP), insulin (INS), C-peptide (C-P), and glucagon (GCG) before and after glucose stimulation in type 2 diabetes mellitus (T2DM) patients with different body mass indexes (BMI), analyze the relevant factors associated with PP secretion, and further investigate the role of PP in the development of obesity and diabetes. Data were collected from 83 patients from the hospital. The subjects were divided into normal-weight group, overweight group, and obese group according to their BMI. All subjects were tested with the standard bread meal test (SBMT). PP and relevant parameters were measured, and the area under the curve (AUC) was calculated after 120min of SBMT. AUCpp (AUC of PP) was used as the dependent variable, and the potential influencing factors were used as independent variables for multiple linear regression analysis. The obese and overweight groups had significantly lower PP secretion than the normal-weight group (485.95 pg·h/ml, 95% CI 76.16-895.74, p = 0.021; 664.61 pg·h/ml, 95% CI 285.46-1043.77, p = 0.001) at 60min postprandial. PP secretion in the obese and overweight groups was also significantly lower than that in the normal-weight group (520.07 pg·h/ml, 95% CI 186.58-853.56, p = 0.003; 467.62 pg·h/ml, 95% CI 159.06-776.18, p = 0.003) at 120min postprandial. AUCpp was negatively associated with BMI (r = -0.260, p = 0.017) and positively associated with AUCGCG (r = 0.501, p< 0.001). Multiple linear regression analysis showed that there was a linear correlation between AUCGCG, BMI, and AUCpp (p< 0.001, p = 0.008). The regression equation was calculated as follows: AUCpp = 1772.255-39.65 × BMI + 0.957 × AUCGCG (R2=54.1%, p< 0.001). Compared with normal-weight subjects, overweight and obese subjects had impaired PP secretion after glucose stimulation. In T2DM patients, PP secretion was mainly affected by BMI and GCG. The Ethics Committee of the Affiliated Hospital of Qingdao University. http://www.chictr.org.cn, identifier ChiCTR2100047486.

Changes in metabolic parameters in ischemic heart disease against the background of metabolic syndrome

For many years, and to this day, cardiovascular disease has been and remains the leading cause of death worldwide. Cardiovascular diseases mainly affect people in countries with middle and low living standards.&#x0D; The aim of the study was to find out the peculiarities of lipid, carbohydrate, and hormonal changes in patients with coronary heart disease against the background of metabolic syndrome.&#x0D; Materials and methods: 120 patients with verified coronary heart disease were examined, including 60 patients with coronary heart disease without metabolic syndrome and 60 patients with coronary heart disease with metabolic syndrome. The control group consisted of 30 practically healthy individuals of appropriate age and sex. The content of HbA1c, glucositol C-peptide, triacylglycerols, total cholesterol, leptin, HDL-cholesterol, and LDL-cholesterol in blood serum was determined by modern methods.&#x0D; Results: The analysis of the results of laboratory tests of patients' blood revealed more pronounced changes in carbohydrate and lipid metabolism in patients with coronary artery disease against the background of metabolic syndrome, which indicates the severity of the clinical course in such patients. The results obtained indicate that in coronary heart disease with metabolic syndrome, there are more pronounced dysmetabolic changes: hyperleptinemia, glucosemia, elevated HbA1c, and decreased C-peptide content. Studies have shown that obesity is accompanied by high levels of leptin, which exacerbates insulin resistance and is a trigger for the development of coronary heart disease.&#x0D; Conclusions: 1. Leptin resistance is a potential cause of insulin resistance and, consequently, obesity, which ultimately leads to metabolic syndrome and the development of coronary heart disease. The data obtained indicate a greater tendency to obesity in women with coronary heart disease complicated by metabolic syndrome.&#x0D; &#x0D; The data obtained may indicate a latent disorder of carbohydrate metabolism in patients with coronary artery disease without metabolic syndrome.&#x0D; The detected deviations in lipid metabolism indicate the presence of type II dyslipoproteinemia in patients of group 1 and type IV dyslipoproteinemia in patients of group 2&#x0D;

Efficacy and Quality of Life Assessment of ‘Kapiva Dia Free Juice’ Treatment as an Adjuvant for Type 2 Diabetes

Background: Diabetes mellitus (DM) is characterized by chronic hyperglycemia, defects in insulin secretion, action, or both, and is fuelled by the obesity epidemic. Conventional medication offers side effects and insufficient glycaemic management in chronic use. Safe and effective adjuvants from the natural source need to be studied clinically. Methods: 30 patients of diabetes mellitus were enrolled in the study for 3 months. The interventional product kapiva dia free juice was administered twice daily along with the conventional antidiabetics. Fasting and post prandial blood glucose were measured every month while HbA1c, serum C-peptide level, BMI, biochemical and hematological investigations on baseline and day 90. Data was analysed using SPSS (version 19). Result: HbA1c was reduced significantly by 11.11% after 90 days of treatment. The percentage of significant reduction in fasting and post prandial blood glucose was 30.05% and 33.11% respectively. BMI was significantly reduced by 2.92% with average weight reduction of 2.17 kg. Insulin resistance was also reduced significantly which was evident by lowered C-Peptide by 28.81%. All the biochemical and hematological parameters were found within normal range and no adverse events were reported related to the investigational product. Conclusion: Kapiva dia free juice is an effective adjuvant treatment in diabetes mellitus which can improve glycemic control, reduce BMI and insulin resistance. This reduces cardiac risk and improves antidiabetic medication effectiveness. All hematological parameters were well within limits in the study which indicates the safety of the product.

The clinical implications of fasting serum insulin levels in patients with insulin-treated type 2 diabetes: a cross-sectional survey.

This study aimed to investigate the clinical implications of fasting serum insulin (FINS) levels in subjects with type 2 diabetes who were receiving insulin therapy. A total of 1,553 subjects with type 2 diabetes [774 subjects who had never received insulin treatment (N-INS) and 779 subjects who were receiving insulin therapy (constant insulin treatment, C-INS)] admitted to the Department of Endocrinology and Metabolism of Peking University People's Hospital were enrolled in this study. Their FINS levels were measured and those with hyperinsulinemia were identified. The underlying mechanisms of hyperinsulinemia were revealed by measuring insulin antibodies (IAs) and analyzing changes in FINS levels before and after polyethylene glycol (PEG) precipitation. In addition, the clinical characteristics of patients with different types of hyperinsulinemia were compared. Higher FINS levels and a higher incidence (43.8%, 341/779) of hyperinsulinemia (FINS >15μIU/mL) were observed in subjects with C-INS than in subjects with N-INS. Among subjects with C-INS and hyperinsulinemia, 66.9% (228/341) were IAs positive, and the incidence of IAs was found to be positively associated with FINS level. By performing PEG precipitation, we found that all subjects without IAs (i.e., those with real hyperinsulinemia) and 31.1% of subjects (71/228) with IAs (i.e., those with both real and IAs-related hyperinsulinemia) still had hyperinsulinemia after PEG precipitation, whereas FINS levels in the other 68.9% of subjects (157/228) with IAs were normal (IAs-related hyperinsulinemia) after PEG precipitation. Comparisons between the groups showed that subjects with real hyperinsulinemia showed more obvious insulin resistance characteristics, including higher lipid levels, BMIs, and homoeostasis model assessment2-estimated insulin resistance (HOMA2-IR) index, and were more likely to have hypertension, obesity, and metabolic syndromes (p<0.05). However, the risk of hypoglycemia and glucose variability increased significantly in subjects with IAs compared with those without IAs. A cutoff of FINS to serum C-peptide ratio (≥9.3μIU/ng) could be used to screen IAs in clinical practice with 83.3% sensitivity and 70% specificity. It is necessary to measure FINS in subjects with C-INS to distinguish between types of hyperinsulinemia, which should help to tailor treatment regimens.