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OBJECTIVE To examine counterregulatory glucose kinetics and test the hypothesis that β-adrenergic blockade impairs these in patients with type 2 diabetes mellitus (T2DM) and advanced β-failure. RESEARCH DESIGN AND METHODS Nine insulin-requiring T2DM subjects and six matched nondiabetic control subjects were studied. β-Cell function was assessed by the C-peptide response to arginine stimulation. Counterregulatory hormonal responses and glucose kinetics were assessed by hyperinsulinemic euglycemic-hypoglycemic clamps with [3-3H]glucose infusion. T2DM subjects underwent two clamp experiments in a randomized crossover fashion: once with infusion of the β-adrenergic antagonist propranolol and once with infusion of normal saline. RESULTS Compared with the control subjects, T2DM subjects had threefold reduced C-peptide responses to arginine stimulation. During the hypoglycemic clamp, glucagon responses were markedly diminished (16.0 ± 4.2 vs. 48.6 ± 6.0 ng/L, P < 0.05), but other hormonal responses and the decrement in the required exogenous glucose infusion rate (GIR) from the euglycemic clamp were normal (−10.4 ± 1.1 vs. −7.8 ± 1.9 µmol · kg−1 · min−1 in control subjects); however, endogenous glucose production (EGP) did not increase (−0.8 ± 1.0 vs. 2.2 ± 0.7 µmol · kg−1 · min−1 in control subjects, P < 0.05), whereas systemic glucose disposal decreased normally. β-Adrenergic blockade in the T2DM subjects increased GIR ∼20% during the euglycemic clamp (P < 0.01), but neither increased GIR during the hypoglycemic clamp or decreased its decrement from the euglycemic clamp to the hypoglycemic clamp. CONCLUSIONS Overall glucose counterregulation is preserved in advanced T2DM, but the contribution of EGP is diminished. β-Adrenergic blockade may increase insulin sensitivity at normoglycemia but does not impair glucose counterregulation in T2DM patients, even those with advanced β-cell failure.

OBJECTIVE To compare the efficacy and safety of the rapid-acting insulin analog glulisine and regular insulin in hyperglycemic hospitalized patients. RESEARCH DESIGN AND METHODS A total of 180 hospitalized patients with type 2 diabetes received either glulisine (n = 88) or regular insulin (n = 92) before each meal in combination with insulin glargine at bedtime in a randomized double-blind fashion. All previous diabetes medications were discontinued if applicable. Doses of insulin were adjusted to obtain target blood glucose concentrations of RESULTS Overall mean blood glucose concentrations were ∼8 mg/dl lower in the glulisine group than in the regular insulin group (152.6 ± 66.6 vs. 160.4 ± 70.8 mg/dl; P < 0.0002). This improvement was wholly due to ∼22 mg/dl lower levels after 4 days of therapy (140 ± 55 vs. 162 ± 71 mg/dl; P < 0.0007); after day 4, this difference progressively increased such that mean blood glucose concentrations from day 7 onward were ∼31 mg/dl lower in the glulisine group. The mean daily incidence of hypoglycemia was slightly but not significantly lower in the glulisine than the regular insulin group (0.10 ± 0.02 vs. 0.14 ± 0.03 episode/day; P > 0.35). CONCLUSIONS In hospitalized type 2 diabetic patients, glulisine may provide better glycemic control than regular insulin, especially in those who have a prolonged length of stay.

Chronic lithium therapy can adversely affect thyroid, parathyroid, and kidney function. We present a 67-year-old man on chronic lithium therapy for bipolar disorder who developed thyroid storm, hypercalcemia, and nephrogenic diabetes insipidus following lithium intoxication. Diagnostic studies revealed no infectious precipitant of thyroid storm, with negative thyroid stimulating immunoglobulin and antithyroid peroxidase antibody levels. Thyroid ultrasound demonstrated small thyroid glands with decreased blood flow, not suggestive of Graves' disease. The patient's symptoms improved on only a few weeks of antithyroid drug and was discharged home without thyroid medications. His thyroid function followed a thyroiditis pattern when it dipped into the hypothyroid range before returning to normal without further interventions. To our knowledge, this is the first reported case of lithium-induced thyroiditis precipitating a thyroid storm and the third reported occurrence of thyroid storm in the context of thyroiditis. The patient's hospital course was further complicated by the development of hypercalcemia and nephrogenic diabetes insipidus requiring specialized treatments. We review the literature on mechanisms and treatment of lithium-induced thyroid dysfunction, hypercalcemia, and diabetes insipidus. Lithium-treated patients should have periodic thyroid function tests, and electrolyte measurements, especially following lithium dose adjustment.