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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Lactic Acidosis in Diabetic Ketoacidosis: A Marker of Severity or Alternate Substrate for Metabolism.

PURPOSE: The lactate level is being increasingly used as a marker of severity of illness and prognosis in multitude of critical conditions. However, its role in diabetic ketoacidosis (DKA) is not well defined. AIM: To determine the prevalence and clinical importance along with the underlying role of metformin in lactic acidosis (LA) in patients admitted with DKA. METHODS: A 2-year prospective and observational study involving 62 consenting in hospital DKA patients. Plasma lactate level on arrival, its clinical significance and relationship with morbidity and mortality in patients with DKA was evaluated. RESULTS: The prevalence of LA (lactate ≥2.5 mmol/l) among the study cohort was found to be 55% with significant LA (≥5 mmol/l) documented in 16%. The median lactate level was 2.55 mmol/l (interquartile range, 1.70-3.20). No significant difference in the severity of LA was seen with metformin use. Lactate correlated positively with initial plasma glucose (IPG) (P = 0.001) and APACHE-II Score (P = 0.002); correlated negatively with systolic blood pressure (P = 0.003), pH (P = 0.002) and severity of DKA (P = 0.001). After controlling for AKI, APACHE II score and blood pressure, lactate continued to correlate positively with IPG (P = 0.002). No mortality or significant morbidity was documented in the entire cohort. CONCLUSIONS: LA has a significant presence in patients with DKA; however, it is not associated with mortality or significant morbidity. Moreover, there was no significant difference in severity of LA with metformin use. Elevated lactate levels may be an adaptation to provide alternate substrate for metabolism in the presence of hypoinsulinemic state. The study results provide rationale for large well-designed studies evaluating in-depth clinical relationship of lactate in DKA.