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27-01: Diabetes Mellitus

Umesh Masharani

Key Clinical Updates in Diabetes Mellitus

Dapagliflozin reduced the risk of end-stage kidney disease or death from renal and cardiovascular causes in a 2020 multinational study of 4304 patients with chronic kidney disease.

The drug was safe and beneficial in patients with eGFR as low as 25 mL/min/1.73 m2.

A third of the patients in the study did not have diabetes and had benefit.

ESSENTIALS OF DIAGNOSIS

Type 1 diabetes

  • Polyuria, polydipsia, and weight loss with random plasma glucose of ≥ 200 mg/dL (11.1 mmol/L).

  • Plasma glucose of ≥ 126 mg/dL (7.0 mmol/L) after an overnight fast, documented on more than one occasion.

  • Ketonemia, ketonuria, or both.

  • Islet autoantibodies are frequently present.

Type 2 diabetes

  • Many patients are over 40 years of age and are obese.

  • Polyuria and polydipsia. Ketonuria and weight loss are uncommon at time of diagnosis. Candidal vaginitis may be an initial manifestation.

  • Plasma glucose of ≥ 126 mg/dL after an overnight fast on more than one occasion. Two hours after 75 g oral glucose, diagnostic values are ≥ 200 mg/dL (11.1 mmol).

  • HbA1c ≥ 6.5%.

  • Hypertension, dyslipidemia, and atherosclerosis are often associated.

EPIDEMIOLOGIC CONSIDERATIONS

An estimated 34.2 million people (10.5%) in the United States have diabetes mellitus, of whom approximately 5–10% have type 1 diabetes and most of the rest have type 2 diabetes. A third group designated as “other specific types” by the American Diabetes Association (ADA) (Table 27–1) number in the thousands. Current statistics about diabetes in the United States are available from the Centers for Disease Control and Prevention (https://www.cdc.gov/diabetes/data/statistics/statistics-report.html).

Table 27–1.Other specific types of diabetes mellitus.
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Table 27–1. Other specific types of diabetes mellitus.

Genetic defects of pancreatic B cell function

 MODY 1 (HNF-4alpha); rare

 MODY 2 (glucokinase); less rare

 MODY 3 (HNF-1alpha); accounts for two-thirds of all MODY

 MODY 4 (PDX1); very rare

 MODY 5 (HNF-1beta); very rare

 MODY 6 (neuroD1); very rare

 Mitochondrial DNA

 Wolfram syndrome

Genetic defects in insulin action

 Type A insulin resistance

 Leprechaunism

 Rabson-Mendenhall syndrome

 Lipoatrophic diabetes

Diseases of the exocrine pancreas

Endocrinopathies

Drug- or chemical-induced diabetes

Other genetic syndromes (Down, Klinefelter, Turner, others) sometimes associated with diabetes

HNF, hepatic nuclear factor; MODY, maturity-onset diabetes of the young; PDX1, pancreatic duodenal homeobox 1.

CLASSIFICATION & PATHOGENESIS

Diabetes mellitus is a syndrome with disordered metabolism and inappropriate hyperglycemia due to either a deficiency of insulin secretion or to a combination of insulin resistance and inadequate insulin secretion to compensate for the resistance.

A. Type 1 Diabetes Mellitus

This form of diabetes is due to autoimmune destruction of pancreatic islet B cell. The rate of pancreatic B cell destruction is quite variable, being rapid in some individuals and slow in others. It occurs at any age but most commonly arises in ...

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