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- How to treat neonatal diabetes mellitus?
Insulin should be used for initial metabolic control in infants with NDM, and
as very small doses of insulin are required in these infants, therapy with
insulin pump may be preferred. Once glycemic control is attained, majority
of patients with KCNJ11 (90 %) and ABCC8 mutations (85 %) can be
switched to sulfonylureas (e.g., glibenclamide). Sulfonylureas bind to SUR1
subunits at β-cell membrane and result in the closure of KAT P channel through
ATP-independent mechanism, thereby promoting insulin secretion.
Glibenclamide is initiated at a dose of 0.05 mg/Kg/day (in divided doses)
and can be titrated, if required. Sulfonylurea therapy is associated with better
glycemic control with lower risk of hypoglycemia as compared to insulin in
infants with NDM. This is attributed to sulfonylurea-mediated improvement
in β-cell sensitivity to incretins.- What is lipodystrophic diabetes?
Lipodystrophic diabetes is a group of metabolic disorders characterized by gen-
eralized or partial wasting/loss of adipose tissue mass, severe insulin resistance,
hyperglycemia, hypertriglyceridemia, and hepatic steatosis. Previously, this
entity was referred as lipoatrophic diabetes; however, this nomenclature was
reframed to lipodystrophic diabetes later, as it refers to the presence of either
lipoatrophy and/or lipohypertrophy in these individuals. Patients with general-
ized lipodystrophy have global loss of fat mass, as opposed to patients with
partial lipodystrophy who have loss of adipose tissue mass in upper half of the
body with accumulation of fat in lower half of the body.- How does lipodystrophy cause diabetes?
Both excess and deficient adipose tissue mass are associated with insulin
resistance and hyperglycemia. Decreased fat mass in patients with lipodystro-
phic diabetes results in a state of leptin deficiency, which in turn leads to
decreased hepatic and peripheral insulin sensitivity via central mechanism
through arcuate nucleus of hypothalamus. In addition, increased circulating
free fatty acids as a result of lack of deposition as triglyceride at eutopic site
(adipocytes) lead to lipotoxicity. Decreased secretion of insulin-sensitizing
adipocytokines (adiponectin) due to paucity of adipocytes further contributes
to insulin resistance.- How to classify lipodystrophic syndromes?
Lipodystrophic syndromes are classified into congenital and acquired lipodys-
trophic syndrome. Congenital lipodystrophy is a result of mutations in genes
responsible for adipocyte differentiation and growth and development, whereas
acquired lipodystrophy is usually drug-induced. The various types of lipodys-
trophies are summarised in the table given below.12 Diabetes in the Young