UNASSIGNED: Determining the cause of hypoglycemia partly relies on blood insulin and C-peptide assays. Although the pancreatic secretion of these peptides is equimolar, discrepancies in their concentrations may occur.
UNASSIGNED: We report the case of a 73-year-old woman with type 2 diabetes mellitus (T2DM) and a history of gastric bypass. The T2DM was initially treated with insulin analogs, which were interrupted due to transient hypoglycemia episodes three years before hospitalization in our endocrinology department. During this hospitalization, the most common etiologies of hypoglycemia were excluded. Fasting insulin level was high (190 mIU/L, reference values (RV): 5-25) on Architect i2000 (an assay recognizing insulin analogs) despite normal blood C-peptide (4.5 μg/L, RV: 0.8-5.2) and slight hypoglycemia (4.5 mmol/L, RV: 4.6-6.1). Insulin level using the Elecsys assay (an assay with low sensitivity to insulin analogs) was very high (>1000 mIU/L, RV: 2.6-24.9). This pattern was observed on several samples, including some taken during a fasting test. Insulin level was only slightly increased using the Mercodia iso-insulin ELISA kit (an assay recognizing insulin analogs). These results excluded an exogenous insulin intake and were suggestive of an interference on insulin assays. To explore the latter possibility, free anti-insulin antibodies were measured and found strongly positive. The presence of interfering insulin-antibody complexes was further investigated using gel filtration chromatography, polyethylene glycol precipitation, and dilution test. Based on these findings, an insulin autoimmune syndrome (IAS) was suspected to cause the hypoglycemic episodes observed.
UNASSIGNED: Although a discrepancy between blood insulin and C-peptide levels points to insulin analog intake, IAS should also be considered, particularly in a patient with transient hypoglycemia. IAS is characterized by the presence of insulin-antibody complexes, which can induce varying degrees of interference on insulin immunoassays and may lead to discordant insulin and C-peptide levels according to the insulin immunoassay used.

BACKGROUND: The relationship between the dietary insulin index (DII) and the disease\'s risk is unknown, despite the fact that hyperinsulinemia is presumed to contribute to osteoporosis. The insulin response of various diets determines the DII. This study aimed to investigate the connection between postmenopausal Iranian women\'s adherence to a diet with a higher insulinemic potential and osteoporosis.
METHODS: A total of 380 postmenopausal women were included in the current case-control study. A 168-item food frequency questionnaire (FFQ) with established validity and reliability was used to evaluate individuals\' daily calorie intake. The standard formula was employed to determine the dietary insulin load of each product. Subsequently, the calculation of DII was performed by dividing the dietary insulin load by the total energy consumed for each individual. In order to investigate the relationship between osteoporosis and DII, logistic regression was implemented.
RESULTS: The results of the current study demonstrated a substantial inverse relationship between osteoporosis and the DII, even after accounting for confounding variables (OR = 0.927; 95% CI = 0.888-0.967). The mean scores of DII (P < 0.001) was significantly higher in control group (36.82 ± 8.98) compared to the case group (33.53 ± 6.28).
CONCLUSIONS: Our findings suggest that keeping a diet high in insulin index and low in foods that are insulinogenic may improve bone mass density. Consequently, it may be essential for postmenopausal women to consume nutrients that stimulate insulin production in order to prevent osteoporosis.

Diazoxide is the only medication approved by the United States Food and Drug Administration for the treatment of hyperinsulinism-induced hypoglycemia. Overdose is infrequently reported. This case describes a preterm four-week-old male who was prescribed diazoxide and chlorothiazide for perinatal stress-induced hyperinsulinism. The patient presented to the emergency department with feeding intolerance and abdominal distension following an accidental 10-fold diazoxide overdose. On presentation, vital signs were remarkable for tachycardia and intermittent tachypnea. Physical exam revealed a grossly distended abdomen. Laboratory abnormalities included a glucose of 216 mg/dL, sodium of 132 mmol/L, and chloride of 98 mmol/L. Abdominal X-ray interpretation found moderate gaseous distension suggestive of generalized ileus. The patient was admitted to the neonatal intensive care unit (NICU), and a nasogastric tube was placed. He received intravenous dextrose fluids, and enteral feeds were resumed as serial X-rays showed interval improvement. The patient remained in the NICU for several days to monitor bowel movements and resolution of ileus and he was discharged after improvement. While diazoxide overdose is rarely reported, and ileus due to such is documented even less frequently, 10-fold medication dose errors are common among infants. The source of the 10-fold mistake is often decimal points, leading zeros, or trailing zeros. Utilizing the smallest possible syringe for the prescribed dose may reduce the incidence of medication errors.

We aimed to investigate the association between an empirical dietary index for hyperinsulinemia (EDIH), empirical dietary index for insulin resistance (EDIR), and MetS and its components in an adult Iranian population. In this cross-sectional study, a total of 6482 participants aged 35-65 years were recruited as part of the MASHAD cohort study. Dietary intakes were assessed using a validated food frequency questionnaire (FFQ). The International Diabetes Federation (IDF) criteria were used to define MetS. Multivariable logistic regression models were applied to determine the association between EDIH, EDIR, and MetS and its components. The mean age and BMI of participants were 48.44±8.20 years, and 27.98±4.73 kg/m2, respectively. Around 59% of the population was female. Of the total population, 35.4% had MetS. According to the full-adjusted model, there was no significant association between higher quartiles of EDIH and EDIR and odds of MetS (Q4 EDIH; OR (95%CI):0.93 (0.74-1.18), Q4 EDIR; OR (95%CI):1.14 (0.92-1.40). Regarding MetS components, EDIR was associated with increased odds of hypertension and diabetes (Q4 EDIR; OR (95%CI):1.22 (1.04-1.44) and 1.22 (1.01-1.47), respectively). EDIH was also associated with decreased odds of hypertriglyceridemia (Q4 EDIH; OR (95%CI): 0.72 (0.60-0.87)). This study showed no significant association between hyperinsulinemia and insulin resistance potential of diet and odds of MetS among Iranian adults. However, EDIR was significantly associated with increased odds of hypertension and diabetes as MetS components.

Diazoxide is a commonly used first-line medication for the treatment of hyperinsulinism. Hyperglycemia may occur with diazoxide use. However, hyperglycemic hyperosmolar state (HHS) secondary to diazoxide is an exceedingly rare but potentially life-threatening adverse effect. We present a case of a 2-year-old with Kabuki syndrome and hyperinsulinism on diazoxide. She presented with 4 days of fever, respiratory symptoms, and lethargy. She was influenza B positive. Initial workup indicated HHS, with an elevated serum glucose (47.1 mmol/L [847.8 mg/dL]; reference range 3.9-6.0 mmol/L; 70-108 mg/dL), serum osmolality (357 mmol/kg H2O; reference 282-300 mmol/kg H2O) but absent urine ketones and no metabolic acidosis (venous pH 7.34). Her course was complicated by an acute kidney injury. Management in the hospital included discontinuation of diazoxide and intravenous fluid resuscitation, following which hyperglycemia and hyperosmolarity resolved. No insulin therapy was required. She remained normoglycemic without diazoxide for 2 weeks but subsequently required restarting of diazoxide for hypoglycemia. This case highlights the need for early recognition and prompt management of diazoxide-related HHS to reduce negative outcomes. We present the first case report of a child with Kabuki syndrome and hyperinsulinism with diazoxide-induced HHS.

To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the various forms of neonatal hypoglycemia and discusses their implications for newborn care. Evidence indicates that all of the major forms of neonatal hypoglycemia are the result of hyperinsulinism due to dysregulation of pancreatic islet insulin secretion. Based on these observations, the authors propose that routine measurement of B-hydroxybutyrate should be considered an essential part of glucose monitoring in newborn infants.

BACKGROUND: Individuals with hyperinsulinemia may initially not meet any diagnostic criteria for metabolic syndrome, though displaying a higher risk of cardiovascular complications combined with obesity, diabetes, and hypertension.
OBJECTIVE: The main objective of our study was to assess the diagnostic accuracy of various cardiovascular risk indices in hyperinsulinemic children and adolescents; a secondary objective was to estimate the optimal cut-offs of these indices.
METHODS: This retrospective single-center study was conducted on 139 patients aged 12.1 ± 2.9 years, managed for hyperinsulinism.
RESULTS: We found statistically significant differences in homeostasis model assessment of insulin resistance index (HOMA-IR), triglyceride glucose index (TyG), TyG-body mass index, visceral adiposity index, lipid accumulation product index, fatty liver index, and hepatic steatosis index. At the linear logistic regression assessment, we found that insulin growth factor-1 (IGF-1), HOMA-IR, and ALT/AST ratio were independently associated with confirmed hyperinsulinism. At the multivariate analysis, IGF-1 levels over 203 ng/mL and HOMA-IR higher than 6.2 were respectively associated with a 9- and 18-times higher odds ratio for hyperinsulinism. The other investigated parameters were not significantly related to hyperinsulinism, and could not predict either the presence of hyperinsulinemia or a subsequent cardiovascular risk in our patients.
CONCLUSIONS: Commonly used indices of cardiovascular risk in adults cannot be considered accurate in confirming hyperinsulinism in children, with the exception of HOMA-IR. Further studies are needed to verify the usefulness of specific cardiovascular risk indices in hyperinsulinemic children and adolescents.

Adipose tissue macrophages (ATMs) influence obesity-associated metabolic dysfunction, but the mechanisms by which they do so are not well understood. We show that miR-6236 is a bona fide miRNA that is secreted by ATMs during obesity. Global or myeloid cell-specific deletion of miR-6236 aggravates obesity-associated adipose tissue insulin resistance, hyperglycemia, hyperinsulinemia, and hyperlipidemia. miR-6236 augments adipocyte insulin sensitivity by inhibiting translation of negative regulators of insulin signaling, including PTEN. The human genome harbors a miR-6236 homolog that is highly expressed in the serum and adipose tissue of obese people. hsa-MIR-6236 expression negatively correlates with hyperglycemia and glucose intolerance, and positively correlates with insulin sensitivity. Together, our findings establish miR-6236 as an ATM-secreted miRNA that potentiates adipocyte insulin signaling and protects against metabolic dysfunction during obesity.

UNASSIGNED: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia.
UNASSIGNED: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing.
UNASSIGNED: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months.
UNASSIGNED: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT.