Serum C-peptide Levels Research Articles

Correlation of Serum C-Peptide, Soluble Intercellular Adhesion Molecule-1, and NLRP3 Inflammasome-Related Inflammatory Factor Interleukin-1β after Brain Magnetic Resonance Imaging Examination with Cerebral Small Vessel Disease

Objective To explore the correlation of serum c-peptide, soluble intercellular adhesion molecule-1 (sICAM-1), and NLRP3 inflammasome-related inflammatory factor interleukin-1β (IL-1β) after brain magnetic resonance imaging (MRI) examination with cerebral small vessel disease (CSVD). Methods A total of 72 CSVD patients treated in our hospital from December 2018 to December 2019 were selected as the case group and another 72 patients who presented cerebrovascular risk factors but obtained normal brain MRI examination result in the same period were selected as the control group. The serum specimen of patients in the two groups were collected, their serum c-peptide levels were measured by radio immunoassay, and their serum sICAM-1 and NLRP3 inflammasome-related inflammatory factor IL-1β were measured by enzyme-linked immunosorbent assay (ELISA), so as to analyze the correlation between these indicators and CSVD. Results Compared with the control group, the level values of serum c-peptide, sICAM-1, and IL-1β were significantly higher in the case group (P < 0.001), with CSVD being the dependent variable, and age, smoking, uric acid, history of stroke, serum c-peptide, sICAM-1, and IL-1β being the independent variables. A logistic regression analysis was conducted, and the result showed that age, smoking, serum c-peptide, sICAM-1, and IL-1β were the risk factors for CSVD, and by drawing the ROC curves, it could be concluded that the area under sICAM-1 curve was larger than that of other single indicator. Conclusion Elevation of level values of serum c-peptide, sICAM-1, and NLRP3 inflammasome-related inflammatory factor IL-1β is correlative with CSVD, and age, smoking, serum c-peptide, sICAM-1, and IL-1β are the independent risk factors for CSVD.

Study of serum C-peptide levels in newly diagnosed diabetic mellitus subjects of North Gujarat region of India

Background: Serum C-peptide has appeared as the chief clinical and practically adequate marker of β-cell function of pancreas. Serum insulin and C-peptide are concomitantly secreted into the blood circulation in equal amount. The aim of the study was to determine serum C-peptide levels in newly diagnosed diabetic mellitus subjects of North Gujarat region of India.Methods:The present cross-sectional study was done on 50 subjects of recently diagnosed Diabetes mellitus (T2DM) and non-diabetic healthy controls at Banas Medical College and our trust-based hospital. All diabetics patients were further classified into two groups; normal FC group consist of subjects with FC level 0.5-3.2 ng/ml (N=14) and high FC group included subjects with FC&gt;3.2 ng/ml (N=36). The patients' demographic and anthropometric parameters were recorded; detailed history and clinical examination were performed in the entire cases. All biochemical parameters were analyzed. Results: Predominance of the T2DM subjects was in the age group of 41-50 years. Mean value for age (p&lt;0.01), anthropometric (p&lt;0.01), fasting plasma glucose (p&lt;0.001), HbA1c (p&lt;0.01), cholesterol (p&lt;0.01), triglycerides (p&lt;0.001) and C-peptide (p&lt;0.001) were significantly higher in the T2DM subjects. The mean values of fasting plasma glucose (p&lt;0.001) and HbA1c (p&lt;0.01) are significantly higher in T2DM subject with high C-peptide level as compared to normal C-peptide level. Conclusions:In our study, we conclude that elevated levels of fasting C-peptide in newly diagnosed T2DM. Therefore, we suggested that serum C-peptide levels are valuable as marker of endogenous insulin production from β-cell of pancreas.

Effects of Serum C-Peptide Level on Blood Lipid and Cardiovascular and Cerebrovascular Injury in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis.

Objective This study aims to investigate the effects of serum C-peptide levels on blood lipid and cardiovascular and cerebrovascular injury in patients with type 2 diabetes mellitus (T2DM). Methods China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Web of Science, and Embase databases were searched for relevant studies published from January 2010 to June 2021. All retrieved randomized controlled trials that evaluated the effect of serum C-peptide levels on blood lipids or cardiovascular and cerebrovascular injuries in T2DM patients were included in our study. Patients in the included studies were divided into normal C-peptide group (control group) and low C-peptide group (treatment group) according to fasting C-peptide levels. Meta-analysis was performed using Stata16.0. Results A total of 7 studies were included for the meta-analysis. Compared with the control group, the treatment group was associated with a higher incidence of coronary heart disease (OR = 4.89; 95% CI: 1.13, 21.24; P < 0.05) and cerebral infarction (OR = 3.24; 95% CI: 0.59, 17.66; P < 0.05). In addition, patients in the treatment group had significantly higher levels of total cholesterol (SMD = 0.01; 95% CI: −0.38, 0.39; P < 0.05), triglyceride (SMD = 0.62; 95% CI: 0.24, 1.00; P < 0.05), glycated hemoglobin (SMD = 0.25; 95% CI: −0.50, 1.00; P < 0.05), and low-density lipoprotein cholesterol (SMD = 0.23; 95% CI: −0.00, 0.46; P < 0.05). However, there was no significant difference in high-density lipoprotein cholesterol levels between the two groups (SMD = 0.30; 95% CI: -0.26, 0.86; P > 0.05). Conclusions Low serum C-peptide level significantly increases the incidence of coronary heart disease and cerebral infarction. Additionally, low serum C-peptide increases blood lipid level and promotes lipid deposition. Collectively, low serum C-peptide has a negative impact on the occurrence and development of T2DM and therefore serum C-peptide level needs to be adjusted timely.

Prevalence and Clinical Profile of Maturity Onset Diabetes of the Young among People with Diabetes Attending a Tertiary Care Centre.

Maturity onset diabetes of young (MODY) is considered to be the most underdiagnosed condition. The correct diagnosis of MODY has a definite bearing on the outcome and clinical course of the disease. We aim to determine the prevalence and clinical profile of MODY among young diabetic patients attending at Department of Endocrinology, a tertiary care institute in North India. It was a cross-sectional study involving all consecutive consenting patients with diabetes and age of onset ≤35 years. A total of 1,094 patients were included in this study, of whom 858 were having age of onset of diabetes <25 years. All patients were screened for MODY using clinical criteria and MODY Probability calculator (available on diabetesgenes.org). Patients with high clinical probability of MODY having negative anti-GAD65 antibody and fasting serum C-peptide levels >0.6 ng/mL were subjected to the Ala98 Val polymorphism (SNP) in hepatocyte nuclear factor (HNF) 1a gene. The prevalence of MODY among the study cohort as per clinical criteria was found to be 7.7%. Males constituted the majority of patients (male vs female, 56% vs. 44%; P < 0.001). The patients with MODY were younger (p < 0.001), leaner (p < 0.001), had younger age at onset of diabetes mellitus (p < 0.001), and lower frequency of features of insulin resistance in the form of skin tags and acanthosis nigricans. Among the 40 patients who were subjected to Ala98Val polymorphism of HNF1α gene (MODY 3), the mutant genotype was seen in 20 (50%) patients. We report a higher prevalence of MODY in our young diabetic patients. A high index of suspicion is required to diagnose MODY as misdiagnosis and inappropriate treatment may have a significant impact on quality-of-life (QOL) with increased cost and unnecessary treatment with insulin.

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.

A multigenerational study on phenotypic consequences of the most common causal variant of HNF1A-MODY

Aims/hypothesisSystematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum.MethodsWe conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT.ResultsHalf of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17–35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m2 units of BMI, p=2.2 × 10−4, using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 μmol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 μmol/l, p=3.1 × 10−5).Conclusions/interpretationThe most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes.Graphical abstract

Clinical Significance of Insulin Peptide-specific Interferon-γ-related Immune Responses in Ketosis-prone Type 2 Diabetes.

Unprovoked A-β+ ketosis-prone type 2 diabetes (KPD) is characterized by the sudden onset of diabetic ketosis/ketoacidosis (DK/DKA) without precipitating factors, negative anti-islet autoantibodies ("A-"), and preservation of β-cell function ("β+") after recovery from DKA. Although this phenotype often appears with acute hyperglycemia and DK/DKA just like acute-onset type 1 diabetes (AT1D), the involvement of anti-islet immune responses remains unknown. We sought to clarify the immunological role of insulin-associated molecules in unprovoked A-β+ KPD. In this cross-sectional study, blood samples from 75 participants (42 with AT1D and 33 with KPD) were evaluated for interferon (IFN)-γ-secreting peripheral blood mononuclear cells (PBMCs) reactive to 4 insulin B-chain amino acid 9-23-related peptides (B:9-23rPep) using an enzyme-linked immunospot (ELISpot) assay. Overall, 36.4% (12/33) of KPD participants showed positive IFN-γ ELISpot assay results; the positivity rate in KPD was similar to that in AT1D (38.1%; 16/42) and statistically significantly higher than the previously reported rate in type 2 diabetes (8%; 2/25; P < .0167). Moreover, B:9-23rPep-specific IFN-γ-producing PBMC frequency was negatively correlated with age and ad lib serum C-peptide levels in all KPD participants and positively correlated with glycated hemoglobin A1c level in KPD participants with positive IFN-γ ELISpot results. These findings suggest the involvement of B:9-23rPep-specific IFN-γ-related immunoreactivity in the pathophysiology of some unprovoked A-β+ KPD. Moreover, increased immunoreactivity may reflect transiently decreased β-cell function and increased disease activity at the onset of DK/DKA, thereby playing a key role in DK/DKA development in this KPD phenotype.

Congenital Hyperinsulinism and Maple Syrup Urine Disease: A Challenging Combination

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. CHI is a challenging disease to diagnose and manage. Moreover, complicating the course of the disease with another metabolic disease, in this case maple syrup urine disease (MSUD), adds more challenges to the already complex management. We report a term neonate who developed symptomatic, non-ketotic hypoglycemia with a blood glucose (BG) level of 1.9 mmol/L at 21-hours of life. A critical sample at that time showed high serum insulin and C-peptide levels confirming the diagnosis of CHI. Tandem mass spectrometry done at the same time was suggestive of MSUD which was confirmed by high performance liquid chromatography. The diagnosis of both conditions was subsequently confirmed by molecular genetic testing. His hypoglycemia was managed with high glucose infusion with medical therapy for CHI and branched chain amino acids (BCAA) restricted medical formula. At the age of four months, a near-total pancreatectomy was done, due to the failure of conventional therapy. Throughout his complicated course, he required meticulous monitoring of his BG and modified plasma amino acid profile aiming to maintain the BG at ≥3.9 mmol/L and levels of the three BCAAs at the disease therapeutic targets for his age. The patient is currently 29 months old and has normal growth and development. This patient is perhaps the only known case of the co-occurrence of CHI with MSUD. Both hypoglycemia and leucine encephalopathy can result in death or permanent neurological damage. The management of CHI and MSUD in combination is very challenging.

Alleviation Effects of GQD, a Traditional Chinese Medicine Formula, on Diabetes Rats Linked to Modulation of the Gut Microbiome.

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Berberine is an insulin secretagogue targeting the KCNH6 potassium channel

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels.

RELATIONSHIPS BETWEEN OSTEOCALCIN LEVEL AND HORMONAL METABOLIC DISORDERS IN TYPE 2 DIABETIC MEN WITH VARIOUS DEGREES OF OBESITY (LITERATURE REVIEW AND OWN RESEARCH)

The bone hormone osteocalcin is formed by osteoblasts and is partially released into the bloodstream during bone resorption, being a biomarker of bone remodeling. Osteocalcin also plays an important role in the endocrine regulation of metabolic and energy processes in the body and in their coordination. Osteocalcin uses a feedback mechanism to regulate insulin secretion, insulin sensitivity of peripheral tissues, and adipokine levels. In general, the secretion of osteocalcin and insulin are important factors in the formation of hormonal-metabolic phenotype, body composition, determination of regional distribution and metabolic activity of both bone and adipose tissue.The aim of this study was to establish the relationship between osteocalcin concentration and hormonal changes in men with type 2 diabetes with and without obesity on the background of involutive changes. Results. 64 men with type 2 diabetes, older than 50 years, were divided into 2 groups by BMI: 1) non-obese, BMI &lt;30 kg / m2 (n = 31); 2) -obese, BMI ≥ 30 kg / m2 (n = 33). Lower levels of insulin secretion (lower serum C-peptide and insulin levels) were observed in non-obese patients in the absence of a compensatory increase in proinsulin levels. It can be assumed that the increase in the concentration of osteocalcin in group 1 is compensatory, although it does not have a significant effect on blood glucose levels. However, it may have a protective effect on the severity of insulin resistance syndrome and related metabolic disorders. Lower levels of osteocalcin in the obese group were associated with a higher degree of insulin resistance and insulin secretion. There was no significant difference between the two groups in serum proinsulin levels, as well as in androgen supply, which was assessed by the levels of total testosterone, testosteronestradiol-binding globulin, and free testosterone index. Conclusion. Lower levels of osteocalcin may be a marker of an increased risk of adverse metabolic changes in obese patients with type 2 diabetes, followed by complications compared to non-overweight patients

Japanese Type 1 Diabetes Database Study (TIDE-J): rationale and study design.

Type 1 diabetes (T1D) is classified into three subtypes: acute-onset, slowly progressive, and fulminant T1D, according to the heterogeneity of clinical course in Japan. Although several cross-sectional databases of T1D have been reported, prospective longitudinal databases to investigate clinical outcomes are lacking in our country. Therefore, we herein construct multi-center prospective longitudinal database of the three subtypes of T1D, accompanied with genetic information and biobanking, which is named Japanese Type 1 Diabetes Database Study (TIDE-J). Inclusion criteria of this study are as follows: (1) the duration of T1D was less than 5years, (2) the patients had one or more islet-related autoantibodies and/or fasting serum C-peptide levels were less than 1.0ng/mL, (3) the patients could clearly understand the study consent in writing. In the TIDE-J, clinical data, including glycemic control, endogenous insulin secretion, islet-related autoantibodies, diabetic complications, and treatment, are collected annually using electric data collection system, which is named REDCap. Furthermore, HLA genotypes of each participant were analyzed at entry and the blood samples were stored for assessing exploratory markers and further genetic analysis annually. The TIDE-J certainly helps in revealing distinct clinical course of each T1D subtype. Moreover, this database may help in identifying novel markers for diagnosing each subtype of T1D and predicting clinical outcomes (including pancreatic beta cell function and disease severity) in patients.

Study on effect of gypenosides on insulin sensitivity of rats with diabetes mellitus via regulating NF-κB signaling pathway

This study focused on the ameliorative effects of gypenosides(GPS) on insulin sensitivity and inflammatory factors in rats with type 2 diabetes mellitus(T2 DM) and explored their possible molecular mechanisms. After the successful establishment of T2 DM model, diabetic rats were randomly divided into four groups, including model group, GPS groups(200, 100 mg·kg~(-1)) and metformin group(100 mg·kg~(-1)), with healthy rats serving as the control. After 6-week intragastric administration, fasting blood glucose(FBG) and oral glucose tolerance were examined. The levels of insulin, C-peptide, tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and C-reactive protein(CRP) in serum were examined. Then the homeostasis model assessment of insulin resistance(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The protein expression levels of phosphorylated insulin receptor substrate-1(p-IRS-1) and phosphorylated protein kinase B(p-Akt) in skeletal muscle were measured by Western blot, as well as those of phosphorylated inhibitor of nuclear factor-κB(NF-κB) kinase β(p-IKKβ), phosphorylated alpha inhibitor of NF-κB(p-IκBα) and phosphorylated p65 subunit of NF-κB(p-p65) in adipose tissue. The relative expression levels of glucose transporter 4(GLUT4) mRNA in skeletal muscle and NF-κB mRNA in adipose tissue were measured by qRT-PCR, and the morphological changes of pancreatic tissue were observed. Compared with the model group, the GPS groups witnessed significant decrease in FBG, marked amelioration of impaired oral glucose tolerance and significant increase in ISI. Further, the high-dose GPS group saw significantly reduced HOMA-IR, TNF-α, IL-1β and CRP, significantly increased expression levels of p-IRS-1(Tyr), p-Akt and GLUT4, and markedly inhibited p-IRS-1(Ser), p-IKKβ, p-IκBα, p-p65 and NF-κB. The concentration of CRP and the expression levels of p-IRS-1(Ser), p-IKKβ, p-IκBα and NF-κB were remarkably reduced in the low-dose GPS group. However, GPS was found less effective in the regulation of serum insulin, C-peptide and IL-6 levels and the alleviation of pancreatic islet injury. The results indicated that GPS can reduce FBG and improve insulin sensitivity in diabetic rats possibly by regulating the NF-κB signaling pathway, inhibiting inflammation, and thereby regulating the expression of key proteins in the insulin signaling pathway.

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...

Transient Neonatal Diabetes Mellitus with the Rare Association of Nonsuppurative Sialadenitis and Genetic Defects in 6q24

Background Transient neonatal diabetes mellitus (TNDM) is the most common cause of diabetes in the first week of life, with an overall incidence of 1 in 90,000 to 160,000 live births. TNDM occurs soon after birth and undergoes spontaneous remission during infancy; however, it may relapse to a permanent form of diabetes mellitus in childhood or adolescence. We report a case of TNDM due to hypomethylation on chromosome 6q24, associated with a rare clinical finding of nonsuppurative submandibular sialadenitis managed by subcutaneous insulin, and who underwent remission by three months of age. Case Presentation. We report a male neonate of Arab ancestry delivered by caesarean section at 37 weeks of gestation. He had intrauterine growth retardation with a birth weight of 2.099 kg. He presented with hyperglycemia on the first day of life, which was managed with parenteral insulin infusion. Blood glucose control was initially difficult to achieve due to difficulties in preparing such small doses of insulin and the significant variations in blood glucose concentrations, without ketosis. Blood tests revealed low serum insulin and C-peptide levels. Genetic analysis revealed multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in chromosome 6q24 and two pathogenic heterozygous variants in the ZFP57 gene. Segregation analysis showed that both parents were heterozygous carriers of familial ZFP57 variants. The clinical course was associated with bilateral nonsuppurative sialadenitis, which is extremely rare among newborns. Conclusion Sialadenitis is a well-known phenomenon that is rarely diagnosed in neonates. To the best of our knowledge, this is the first case report to describe the exceedingly rare association of nonsuppurative submandibular sialadenitis in a neonate with TNDM due to multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in 6q24 and heterozygous pathogenic variants in the ZFP57 gene.

Safety and Feasibility of Fasting-Mimicking Diet and Effects on Nutritional Status and Circulating Metabolic and Inflammatory Factors in Cancer Patients Undergoing Active Treatment

Simple SummaryOur phase I/II clinical trial demonstrated that periodic cycles of a modified fasting regime (“fasting-mimicking diet” (FMD) by L-Nutra) were feasible and safe in cancer patients at low nutritional risk and that they did not negatively affect the patients’ body composition when combined with dietary and muscle training instructions to promote lean body mass re-gain in the periods between FMD cycles. While previously published studies of modified fasting in cancer patients exclusively enrolled patients receiving chemotherapy, in our trial, we also accrued patients treated with different types of therapies, including endocrine therapies (w/ or w/o CDK4/6 inhibitors), TKIs, proteasome inhibitors, immune check point inhibitors and radiotherapy. Eighteen different types of cancer are represented in our trial. Our study also shows that the FMD decreased fat mass and effectively lowered the circulating insulin, IGF1 and leptin. These are important elements of novelty of our study when compared to previously published trials.In preclinical studies, fasting was found to potentiate the effects of several anticancer treatments, and early clinical studies indicated that patients may benefit from regimes of modified fasting. However, concerns remain over possible negative impact on the patients’ nutritional status. We assessed the feasibility and safety of a 5-day “Fasting-Mimicking Diet” (FMD) as well as its effects on body composition and circulating growth factors, adipokines and cyto/chemokines in cancer patients. In this single-arm, phase I/II clinical trial, patients with solid or hematologic malignancy, low nutritional risk and undergoing active medical treatment received periodic FMD cycles. The body weight, handgrip strength and body composition were monitored throughout the study. Growth factors, adipokines and cyto/chemokines were assessed by ELISA. Ninety patients were enrolled, and FMD was administered every three weeks/once a month with an average of 6.3 FMD cycles/patient. FMD was largely safe with only mild side effects. The patients’ weight and handgrip remained stable, the phase angle and fat-free mass increased, while the fat mass decreased. FMD reduced the serum c-peptide, IGF1, IGFBP3 and leptin levels, while increasing IGFBP1, and these modifications persisted for weeks beyond the FMD period. Thus, periodic FMD cycles are feasible and can be safely combined with standard antineoplastic treatments in cancer patients at low nutritional risk. The FMD resulted in reduced fat mass, insulin production and circulating IGF1 and leptin. This trial was registered on Clinicaltrials.gov in July 2018 with the identifier NCT03595540.

Insulin Resistance Is Not Increased in Inflammatory Bowel Disease Patients but Is Related to Non-Alcoholic Fatty Liver Disease.

Background. Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods. Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results. Neither HOMA2-IR (beta coef. −0.26 {95%CI −0.64–0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI −14–44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2—B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = <0.001). Conclusions. IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD.

Antidiabetic and Antilipidemic activity of Poly herbal formulation (PHF) in STZ-NA induced diabetes in rats

The effects of polyherbal formulations were studied in the streptozotocin-nicotinamide (STZ-NA) induced diabetes rat model. The present study was undertaken to assess the effects of polyherbal formulations on the blood sugar level (BSL) as well as blood lipid level(BLL) of STZ-NA diabetic rats. The leaves of Moringa oleifera and roots of Raphanus raphanistrum were used for the study due to the presence of various phytoconstituents such as alkaloids, saponins, tannins, steroids, phenolic acids, flavonoids. Three polyherbal formulations were prepared from different portions of leaves of Moringa oleifera and roots of Raphanus raphanistrum and titled PHF-I, PHF-II and PHF-III. Diabetes in experimental animals was induced by STZ injection intraperitoneally (i. p) after 30 min of Nicotinamide injection i. p in all animal groups except normal control group animals. Group, I served as normal control received no treatment. Group II served as negative control received streptozotocin-nicotinamide. Group III rats were treated with Metformin, Group IV, Group V and Group VI rats treated with PHF-I, PHF-II and PHF-III respectively. Physical parameters (body weight, feed and water intake), Biochemical parameters (Blood Glucose, Serum Insulin, Serum C-Peptide Level, Serum Leptin, Serum Total cholesterol, Serum Triglycerides, LDL and VLDL) were measured on 0th, 14th and 28th day. The study results and histopathology of the pancreas indicate that oral administration of polyherbal formulation- II proved as a more effective, safe anti-diabetic agent in comparison to Polyherbal formulation I and III by Decrease in body weight, fasting blood glucose, serum glucose level. Increase in serum insulin level, serum C-peptide with a significant decrease in blood serum lipid level.

Amylin serum levels are upregulated in patients with systemic lupus erythematosus.

Amylin is a pancreatic hormone that participates in glucose homeostasis. We aimed to investigate how serum amylin levels are expressed in patients with systemic lupus erythematosus (SLE) compared to matched controls, and their possible relationship to disease-related characteristics, such as activity or damage. 144 SLE patients and 96 non-diabetic sex- (female 96% vs. 91%, p=0.43) and age-matched controls (49±11 vs. 51±8 years, p=0.09) were included. Amylin, insulin and C-peptide serum levels, as well as insulin resistance indexes were assessed in both groups. Multivariable regression analysis was performed to compare amylin between groups and to explore its interrelations with SLE features. The analyses were adjusted for glucocorticoids intake and for insulin resistance classic risk factors. Patients with SLE exhibited significant higher serum levels of amylin when compared to controls after multivariable analysis (beta coef. 1.56 [95%CI 1.01-2.11], p=0.000). Moreover, SLE patients not on prednisone (beat coef. 1.54 [95%CI 0.98-2.10] ng/ml, p=0.000) and those on prednisone (beta coef. 1.51 [95%CI 0.96-2.07] ng/ml, p=0.000) disclosed higher amylin serum levels compared to controls in the fully multivariable analysis. Hyperamylinaemia in SLE patients remained significant even adjusting for differences in the insulin resistance and beta cell production rates between patients and controls. The damage produced by the disease and its severity were independently and positively associated with amylin serum levels. Amylin is upregulated in SLE patients compared to controls, regardless of the insulin resistance that SLE may present. The damage produced by the disease and its severity independently explains this upregulation.

C-Peptide

Objective: C-peptide has been the most technically appropriate and theoretically reasonable substitute for β-cell activity. In equimolar concentration, insulin and C-peptide are co-secreted into the portal circulation. Methods: A total of 150 participants of diagnosed diabetes mellitus (DM) and 18–45 years aged were studied. Those diabetics were classified into three groups supported by fasting serum C-peptide (FC) level and low FC cluster comprised participants with FC level &lt;0.6 ng/ml. Intermediate FC group comprised subject with FC level &gt;0.6–1.8 ng/ml and high FC group comprised participants with FC &gt;1.8 ng/ml. Results: The cutoff set of C-peptide was taken as 0.3–2.45 ng/ml. The prevalent diabetes among males was 85%–65% female. For the 150 diabetic participants, 18 (12%) were classified as type 1 DM (T1DM), 77 (51.3%) with type 2 DM, and the rest 55 (36.7%) as latent autoimmune diabetes in adults or MODY were perceived. In participants with T1DM, the mean serum C-peptide was slightly lower than in other diabetes forms. Considering the family history of diabetics in our research, detectable C-peptide in people with the family experience of diabetes was identified. Family diabetes history presence was seen in 15.5% of type 1 DM T1DM cases, while 84.5% of the remainder of the cases. Such classification is focused solely on family records and C-peptide rates which are subject to antibody screening, a genetic study for improved identification of the forms of diabetes. Conclusions: This result indicates that the diabetes measure C-peptide should be used in scientifically linked diabetes diagnosis, diabetes period, and subject age for appropriately managing persons with diabetes.