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The pathophysiology of brain damage induced by severe hypoglycemia is still unknown. We experienced a case with type 1 diabetes and recurrent severe hypoglycemic coma who showed a central brain atrophy and an abnormal cerebrospinal fluid flow, suggesting normal pressure hydrocephalus. Following this case, the CSF flow was studied using 111In-DTPA cisternography in six consecutive diabetic patients admitted for repeated episodes of hypoglycemic coma. All the patients showed the central brain atrophy on computed tomography and four of them (67%) had the ventricular reflux, with delayed clearance of 111In-DTPA. Two patients with abnormal CSF flow showed cognitive dysfunction by WAIS or WAIS-R. In contrast, none of five randomly selected diabetic patients, without hypoglycemic coma showed abnormal CSF flow. Our results suggest the presence of normal pressure hydrocephalus in diabetic patients with recurrent hypoglycemic coma. It may associate with the cognitive dysfunction.

The substitution of guanine for adenine at position 3243 of the leucine tRNA gene of mitochondrial DNA was originally described in association with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Diabetes mellitus associated with the mutation (mitochondrial diabetes) is a different phenotype from MELAS. We identified 11 patients with the mutation among 385 Japanese diabetic patients: two had MELAS and nine had mitochondrial diabetes. We present data on a male patient with mitochondrial diabetes who developed the nephrotic syndrome at the age of 23. Light microscopy revealed mesangial expansion, PAS-positive deposits and segmental sclerosis in the glomeruli. Scattered mesangial electron-dense deposits and thickening of the basement membrane were found on electron microscopy, suggesting that diabetic glomerulosclerosis accompanied by focal glomerulosclerosis (FGS). Mitochondrial diabetes may pre-dispose patients to renal complications, including forms of glomerulonephritis, such as FGS.

We compared the renoprotective effect between angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine-type calcium channel blocker, nicardipine, in a severe form of renal injury in rats. Two-day-old spontaneously hypertensive rats (SHR) were injected with streptozotocin or vehicle as control. UNX was performed at 3 weeks of age, and enalapril or nicardipine was administered in drinking water from 7 weeks of age. Uninephrectomy (UNX) markedly exacerbated hypertension and renal injury in the nondiabetic and diabetic SHR. Enalapril and nicardipine comparably reduced blood pressure in UNX diabetic SHR. However, serum creatinine was significantly elevated in the nicardipine-treated group as compared with the enalapril-treated group at 24 weeks of age (nicardipine-treated group, 67 +/- 4 microM; enalapril-treated group, 49 +/- 3 microM; P < 0.01; untreated group 57 +/- 4 microM). Furthermore, the incidence of glomerular sclerosis was similar between untreated and nicardipine-treated groups, whereas it tended to be reduced in the enalapril-treated group. In a separate experiment of diabetic SHR without UNX, enalapril therapy significantly ameliorated hyperglycemia and albuminuria (P < 0.01). This study showed that a renoprotective effect was seen in enalapril but not in nicardipine in UNX diabetic SHR despite the comparable reduction of blood pressure. This suggests that enalapril may be more effective than nicardipine in delaying the progression of a severe form of diabetic nephropathy.

We studied a circadian blood pressure variation in relation to the progression of diabetic nephropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Age, duration of diabetes, body mass index and glycemic control did not differ among the groups of patients with normo-, micro- and macroalbuminuria. None of the patients received antihypertensive drugs. There were no differences in renal and autonomic functions between normo- and microalbuminuric groups, but these functions were impaired in the macroalbuminuric group. The rise in blood pressure was more apparent in 24-h ambulatory blood pressure (AMBP), especially during night-time, as compared with casual blood pressure. Such blood pressure rise was in accordance with the progression of nephropathy. However, pulse rate did not differ among the three groups. The nocturnal fall in blood pressure was blunted in the micro- and macroalbuminuria groups, but evident in the normoalbuminuric group. In the latter, daytime systolic blood pressure (SBP) was significantly higher than night-time SBP (123 +/- 5 mmHg vs. 113 +/- 3 mmHg, P = 0.002). In contrast, in the former two groups of patients, there were no significant differences in SBP between daytime and night-time (134 +/- 9 mmHg vs. 134 +/- 9 mmHg, ns, for microalbuminuria and 159 +/- 8 mmHg vs. 165 +/- 7 mmHg, ns, for macroalbuminuria). Urinary albumin excretion was significantly correlated with night-time SBP (r = 0.48, P = 0.015), but not with daytime SBP (r = 0.30, ns).(ABSTRACT TRUNCATED AT 250 WORDS)