Delayed hypopituitarism following Russell's viper envenomation: a case series and literature review.

PURPOSE: Hypopituitarism (HP) is an uncommon consequence of Russell's viper envenomation (RVE). Delayed hypopituitarism (DHP) presents months to years after recovering from snake bites (SB). The clinical presentation, manifestations, and outcomes of DHP following RVE have not been systematically studied. Here, we present a case series of HP following RVE with delayed diagnosis and conduct a literature review. METHODS: We retrospectively reviewed data of eight DHP cases and literature to outline the presentation, manifestations, hormonal profiles, and radiological features of DHP following RVE. RESULTS: Three men and five women, with a mean age at diagnosis of 39.5 ± 11.6 years, were included. The mean duration between snake bite (SB) and HP diagnosis was 8.1 ± 3.6 years. Secondary hypothyroidism and hypogonadotropic hypogonadism were present in all patients. Growth hormone deficiency (GHD) and secondary hypocortisolism were present in 6 (75%) patients. Magnetic resonance imaging (MRI) revealed empty sella and partially empty sella in three patients each (75%). The literature review revealed additional 20 DHP cases (mean age at diagnosis 32.4 ± 10.8 years), with 65% of patients being men. Fatigue, reduced libido, and loss of weight were the commonest symptoms among men. Secondary amenorrhea, fatigue, and loss of appetite were common manifestations among women. Acute kidney injury, GHD, secondary hypothyroidism, hypogonadism, and adrenal insufficiency were reported in 75%, 79%, 95%, 100%, and 85% of patients, respectively. CONCLUSIONS: DHP is an important complication of RVE, and a delay in its diagnosis is associated with significant morbidity. Patients with RVE should be followed up for a long term to identify DHP.

Continuous Glucose Monitoring for the Detection of Hypoglycemia in Patients With Diabetes of the Exocrine Pancreas.

BACKGROUND: Detailed evaluations of hypoglycemia and associated indices based on continuous glucose monitoring (CGM) are limited in patients with diabetes of the exocrine pancreas. Our study sought to evaluate the frequency and pattern of hypoglycemic events and to investigate hypoglycemia-specific indices in this population. METHODS: This was a cross-sectional study comprising 83 participants with diabetes of the exocrine pancreas. CGM and self-monitoring of blood glucose (SMBG) were performed on all participants for a minimum period of 72 hours. The frequency and pattern of hypoglycemic events, as well as hypoglycemia-related indices, were evaluated. RESULTS: Hypoglycemia was detected in 90.4% of patients using CGM and 38.5% of patients using SMBG. Nocturnal hypoglycemic events were more frequent (1.9 episodes/patient) and prolonged (142 minutes) compared with day-time events (1.1 episodes/patient; 82.8 minutes, P < 0.05). The mean low blood glucose index was 2.1, and glycemic risk assessment diabetes equation hypoglycemia was 9.1%. The mean time spent below (TSB) <70 mg/dL was 9.2%, and TSB <54 mg/dL was 3.7%. The mean area under curve (AUC) <70 mg/dL was 1.7 ± 2.5 mg/dL/hour and AUC <54 mg/dL was 0.6 ± 1.3 mg/dL/hour. All of the CGM-derived hypoglycemic indices were significantly more deranged at night compared with during the day (P < 0.05). CONCLUSION: Patients with diabetes of the exocrine pancreas have a high frequency of hypoglycemic episodes that are predominantly nocturnal. CGM is superior to SMBG in the detection of nocturnal and asymptomatic hypoglycemic episodes. CGM-derived hypoglycemic indices are beneficial in estimating the risk of hypoglycemia.

Comparison of CGM-Derived Measures of Glycemic Variability Between Pancreatogenic Diabetes and Type 2 Diabetes Mellitus.

BACKGROUND: To compare glycemic variability (GV) indices between patients with fibrocalculous pancreatic diabetes (FCPD) and type 2 diabetes mellitus (T2D) using continuous glucose monitoring (CGM). METHODS: We measured GV indices using CGM (iPro™2 Professional CGM, Medtronic, USA) data in 61 patients each with FCPD and T2D who were matched for glycated hemoglobin A1c (HbA1c) and duration of diabetes. GlyCulator2 software was used to estimate the CGM-derived measures of GV (SD, mean amplitude of glycemic excursion [MAGE], continuous overall net glycemic action [CONGA], absolute means of daily differences [MODD], M value, and coefficient of variance [%CV]), hypoglycemia (time spent below 70 mg/dL, AUC below 70 mg/dL, glycemic risk assessment diabetes equation hypoglycemia, Low Blood Glucose Index), and hyperglycemia (time spent above 180 mg/dL at night [TSA > 180], AUC above 180 mg/dL [AUC > 180], glycemic risk assessment diabetes equation hyperglycemia, High Blood Glucose Index [HBGI], and J index). The correlation of GV indices with HbA1c, duration of diabetes, and demographic and biochemical parameters were also assessed. RESULTS: All the CGM-derived measures of GV (SD, MAGE, CONGA, MODD, and %CV), except M value, were significantly higher in the FCPD group than in the T2D group (P < 0.05). Measures of hyperglycemia (TSA >180, AUC >180, HBGI, and J index) were significantly higher in the FCPD group than in the T2D group (P < 0.05). The measures of hypoglycemia were not significantly different between the two groups. All the hyperglycemia indices showed a positive correlation with HbA1c in both groups. CONCLUSIONS: FCPD is associated with higher GV than is T2D. The findings of higher postprandial glycemic excursions in patients with FCPD could have potential therapeutic implications.

Prevalence of hypogonadism in patients with type 2 diabetes mellitus among the Indian population.

OBJECTIVES: To determine the prevalence of hypogonadism among Indian men with and without type 2 diabetes mellitus (T2DM) and evaluate its association with various metabolic parameters. METHODS: One hundred fifty consecutive men with T2DM, aged 25-70 years, and one hundred age-matched healthy men without diabetes were included. The free testosterone (FT) level was calculated using the total testosterone (TT), sex hormone-binding globulin (SHBG), and albumin levels in serum. Patients with a calculated FT level <6.35 ng/dL and a positive response on the androgen deficiency in aging male questionnaire (ADAM) were diagnosed with hypogonadism. RESULTS: The prevalence of hypogonadism was 17.3% and 10% in men with and without T2DM, respectively. The body mass index (BMI) and the mean levels of follicle-stimulating hormone (FSH), TT, SHBG, Triglycerides (TG), and FT were significantly different between the groups. The mean BMI and TG levels were significantly higher in patients with T2DM than in those without. Both groups showed a significant negative correlation between the BMI and SHBG level. CONCLUSION: The hypogonadism prevalence was higher in patients with T2DM than in those without, although the difference did not reach statistical significance.

Association of total and calculated free testosterone with androgen deficiency symptoms in patients with type 2 diabetes.

The Androgen Deficiency in the Aging Male (ADAM) questionnaire is commonly used to screen type 2 diabetes mellitus (T2DM) patients for androgen deficiency symptoms, but the association of low total (TT) and free testosterone (FT) levels with divergent responses to the ADAM questionnaire remains unclear. The aim of this study was to assess the predictive ability of TT and calculated FT (cFT) levels for accurately classifying ADAM status. We recruited 70 patients each with positive (group A) and negative (group B) responses to the ADAM questionnaire and 70 age-matched healthy controls (group C) (mean age, 50.5 years); serum levels of TT were estimated and cFT were estimated using Vermeulen equation. Hypogonadism was defined as the presence of symptoms (positive ADAM score) along with TT level < 300 ng/dL or calculated (cFT) <6.35 ng/dL. BMI was highest in group A (P < 0.05), followed by groups B and C. Group A had longer diabetes durations (P < 0.05) and higher fasting plasma glucose (FPG) and HbA1c levels than group B (P < 0.001). TT levels and cFT were significantly lower in Group A than in the other two groups. In group A, 51 (73%) men had low TT levels (<300 ng/dL) and 48 (69%) had low cFT (<6.35 ng/dL). TT levels < 300 ng/dL had higher sensitivity and specificity (73 and 96%, respectively) than cFT < 6.35 ng/dL (69 and 90%, respectively) for predicting ADAM status. Multivariate-adjusted logistic regression showed that diabetes duration, HbA1c level, and BMI predicted low TT levels, whereas diabetes duration and HbA1c and high-density lipoprotein levels were significant predictors of low cFT. TT levels were a better predictor of ADAM responses than cFT in male T2DM patients. Our results suggest that TT level is better than cFT for diagnosing hypogonadism in T2DM patients when equilibrium dialysis is not feasible.

A comparative study of the clinical profile of fibrocalculous pancreatic diabetes and type 2 diabetes mellitus.

AIMS: The present study aimed to compare the clinical characteristics of patients with fibrocalculous pancreatic diabetes (FCPD) and those with type 2 diabetes mellitus (T2DM) to identify the characteristics distinctive of FCPD. METHODS: A total of 133 patients with FCPD were compared with 665 patients with T2DM matched for duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular and macrovascular complications in both groups. RESULTS: The mean duration of diabetes was 4.42 ±â€¯5.65 years in the FCPD group and 4.51 ±â€¯3.88 years in the T2DM group. FCPD participants were significantly younger at diagnosis and leaner than patients with T2DM. The FCPD group had higher fasting and postprandial glucose and HbA1c levels than the T2DM group. The FCPD group had significantly lower triglyceride, total cholesterol, low-density lipoprotein cholesterol, serum total calcium, hemoglobin, and serum creatinine values than the T2DM group. The prevalence of coronary artery disease, stroke, and retinopathy was significantly higher in the T2DM patients while the prevalence of distal symmetric polyneuropathy was significantly lower. On multivariate logistic regression analysis, duration of diabetes and HbA1c (OR = 1.17, P = 0 0.04) in FCPD patients and age (OR = 1.04, P < 0 0.001), duration of diabetes (OR = 1.17, P < 0 0.001) and HbA1c (OR = 1.28, P < 0.001) in T2DM patients were associated with microvascular complications. CONCLUSIONS: There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM. Timely diagnosis may have implications in the follow-up and management of patients.

Assessment of insulin sensitivity and secretion in patients with fibrocalculous pancreatic diabetes.

Background: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes seen in patients with tropical chronic pancreatitis. Insulin deficiency plays a major role in the etiopathogenesis of FCPD. Limited data suggest a possible role of insulin resistance (IR) in the pathogenesis of FCPD. Sparse data exist on measures of insulin sensitivity (IS) and secretion in patients with FCPD and its comparison to type 2 diabetes mellitus (T2D) patients. Method: Eighty patients with FCPD, 36 patients with T2D and 36 healthy subjects were included. A 75 g oral glucose tolerance test (OGTT) was performed in the morning after an overnight fast. We evaluated IS and secretion using indices derived from fasting (homeostasis model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI] and homeostasis model assessment of beta-cell function [HOMA-ß]) and OGTT (Matsuda, insulin sensitivity index by Kanauchi [ISI-K], oral glucose insulin sensitivity index [OGIS], Stumvoll, insulinogenic index and oral disposition index [ODI]) measurements of glucose and insulin. Results: HOMA-IR was significantly higher and QUICKI significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001). Matsuda, ISI-K, OGIS and Stumvoll were significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001), indicating reduced IS in both FCPD and T2D patients. HOMA-ß, insulinogenic index and ODI were significantly lower in patients with FCPD and T2D compared to healthy controls (P<0.001). Conclusion: FCPD is associated with reduced IS as assessed by fasting and OGTT-based indices. FCPD is also associated with a greater degree of impairment in insulin secretion than in T2D. IR may play a role in the pathogenesis of FCPD.

Clinical correlates of sudomotor dysfunction in patients with type 2 diabetes and peripheral neuropathy.

AIMS: To investigate the factors associated with abnormal electrochemical skin conductance (ESC) in patients with type 2 diabetes mellitus (T2D) and early diabetic peripheral neuropathy (DPN). METHODS: We recruited 523 consecutive patients with T2D (median age: 50 [interquartile range: 16] years; median T2D duration: 4 [5] years). Sudomotor dysfunction was defined as an ESC <60 µS, and DPN as a neuropathy disability score (NDS) ≥6. Logistic regression was performed to determine the predictors of sudomotor dysfunction in patients with DPN. RESULTS: The prevalence of sudomotor dysfunction was 29% for all patients and 84.5% for patients with DPN. A significant negative correlation was observed between the NDS and ESC measurements (r = -0.52, p < 0.0001). In the univariate analysis, abnormal ESC measures were associated with age, diabetes duration, glycated hemoglobin, diabetic retinopathy, insulin therapy, and foot abnormalities. In the multivariate analysis, ESC abnormalities were associated with age, diabetes duration, glycated hemoglobin levels, insulin therapy, and foot deformities. There was a robust association between foot deformities and abnormal ESC (p = 0.049; odds ratio = 16.02) in patients with DPN. CONCLUSION: Sudomotor dysfunction is highly prevalent in patients with T2D, especially in those with DPN. Various diabetes-related factors were linked to lower ESC values, indicating an association between chronic hyperglycemia and sudomotor function. We also observed a strong relationship between foot deformities and ESC abnormalities. We conclude that the factors associated with DPN are also relevant to sudomotor dysfunction.