Delayed onset Bickerstaff brainstem encephalitis overlapping Miller-Fisher Syndrome during SARS-CoV-2 infection.

Bickerstaff brainstem encephalitis (BBE) is a neuroimmunologic disease characterized by the acute onset of external ophthalmoplegia, ataxia, and consciousness disturbance, mostly subsequent to an infection. BBE is considered to be a variant of Miller-Fisher syndrome (MFS), which also exhibits external ophthalmoplegia and ataxia but not presenting consciousness alterations. Therefore, these two medical conditions are included in the clinical spectrum of the "Fisher-Bickerstaff syndrome" ( Shahrizaila and Yuki in J Neurol Neurosurg Psychiatry 84(5):576-583) [1]. With regard to the etiopathogenesis, increasing evidence worldwide suggests that SARS-CoV-2 infection-enhanced immune response is involved in a wide range of neurological complications such as Guillain-Barré syndrome (GBS), MFS, acute necrotizing encephalitis (ANE), myelitis, acute disseminated encephalomyelitis (ADEM), and, although very rarely, BBE either (Hosseini et al. in Rev Neurosci 32:671-691) [2]. We report a case of a patient affected by delayed onset BBE overlapping MFS during a mild SARS-CoV-2 infection. To the best of our knowledge, similar cases have never been reported.

Indications and results of videocapillaroscopy in clinical practice.

Nailfold videocapillaroscopy (NVC) is one of the best diagnostic non-invasive imaging techniques to evaluate microcirculation in vivo and is increasingly employed in the field of rheumatology. Indeed, at present, the most important utility of NVC is in the identification of microvascular involvement in many rheumatic diseases, particularly in systemic sclerosis. More recently, this technique has been shown to be applicable to the study of many other extra-rheumatic diseases, such as arterial hypertension, diabetes mellitus, acromegaly, hyperthyroidism, cardiac syndrome X, primary biliary cirrhosis, Crohn's disease, psoriasis, familial Mediterranean fever. This article sets down the methodology of examination and normal pattern of capillary vessels and reviews the applications of NVC in clinical practice and its results in rheumatic and non-rheumatic diseases.

Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.

BACKGROUND: Postprandial plasma glucose (PPG) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications. Older persons with type 2 diabetes mellitus (DM2) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics, the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline. METHODS: Two groups of aged diabetic patients were randomly selected to be treated with repaglinide (n = 77) or glibenclamide (n = 79). RESULTS: Coefficient of variation of PPG (CV-PPG) was associated with Mini-Mental State Examination (MMSE) scores (r = -0.3410; p < 0.001) and a composite score of executive and attention functioning (r = -0.3744; p < 0.001) after adjusting for multiple confounders. Both groups showed a significant decline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), but only the repaglinide group demonstrated a significant decline of CV-PPG over time. In models investigating the change in cognitive functioning over time, adjusted for HbA1c and CV-FPG, a decline in cognitive functioning was observed only in the glibenclamide group (p < 0.001). After adjusting for CV-PPG, the authors no longer found a decline in executive and attention functioning composite score (p = 0.085) or the MMSE (p = 0.080) with glibenclamide. CONCLUSIONS: Exaggerated postprandial glucose (PPG) excursions are associated with a derangement of both global, executive, and attention functioning. A tighter control of PPG may prevent cognitive decline in older diabetic individuals.

Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors.

The combined effect of Peroxisome proliferator-activated receptor gamma (PPARG) Pro/Ala and interleukin-6 G174C gene variants, was evaluated in 429 Caucasian subjects in order to determine whether subjects carrying both variants were at different risk for obesity. In particular, the combined contribution of these two variants (both independent and interaction effects) to the total variation of obesity-related factors was estimated. All subjects were genotyped for codon 12 Pro/Ala locus variability and for the interleukin-6-174 C/G promoter polymorphism. Subjects with the Ala variant had significantly lower BMI, insulin resistance, triglyceride levels than those without. Furthermore, subjects with Ala variant had significantly lower IL-6 levels (0.88 +/- 0.9 vs 1.61 +/- 2.25 pg/ml; p = 0.041). In contrast, the IL6-C variant was significantly associated with lower plasma IL-6 and with lower total cholesterol levels but was not significantly associated with any other obesity risk factors. Indeed, subjects carrying both PPARG and IL-6 gene variants, had a clearly more favourable profile of obesity related risk factors than subjects with one variant, having Ala+/C+ carriers lower BMI (22.8 +/- 2.3 vs 24.14 +/- 1.9; f = 5.31; p < 0.005), insulin resistance (1.49 +/- 0.70 vs 2.13 +/- 0.92; f = 4.342; p = 0.038) and triglyceride levels (79.15 +/- 32.9 vs 98 +/- 6.73 mg/dl; f = 3.120; p < 0.005). These findings suggest that the effect of the two genetic variants on 'obesity related' factors is additive.

Effects of perindopril and carvedilol on endothelium-dependent vascular functions in patients with diabetes and hypertension.

OBJECTIVE: To compare the effects of the ACE inhibitor perindopril and the beta-blocker carvedilol on blood pressure and endothelial functions in NIDDM patients with hypertension. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4-8 mg daily) or carvedilol (25-50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide. RESULTS: Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05-0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group. CONCLUSIONS: At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.

Hemodynamic and metabolic effects of transdermal clonidine in patients with hypertension and non-insulin-dependent diabetes mellitus.

The aim of this study was to evaluate the effect of transdermal clonidine on hemodynamic and metabolic parameters in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in placebo period, 20 NIDDM patients who had diastolic blood pressure in the range of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled, cross-over study of 4 week treatment with clonidine (transdermal patch 2.5 mg/week) or placebo (inactive patch). Compared with placebo, clonidine significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v 98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99 +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P < .01). Oxidative glucose disposal (indirect calorimetry) was also greater after clonidine. Plasma glucose, insulin, and C-peptide responses following oral glucose (75 g) were significantly lower after clonidine, as well as urinary albumin excretion. Transdermal clonidine is effective in reducing blood pressure in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce the cardiovascular impact of hypertension in diabetes mellitus.

L-arginine for testing endothelium-dependent vascular functions in health and disease.

The objective of this study was to assess the role of L-arginine, the natural precursor of nitric oxide, for testing endothelial function in physiological and pathophysiological conditions. In an initial study of 20 healthy subjects, mean blood pressure decreases in response to increasing doses of L-arginine (1, 2, 3, and 5 g) were 1.1 +/- 1.3, 2.6 +/- 1.5, 7.6 +/- 1.3, and 7.7 +/- 2 mmHg, respectively, P < 0.01. The enantiomer D-arginine (3 g) did not produce any change in mean blood pressure and platelet aggregation (n = 10), whereas the infusion of the L-arginine analog NG-monomethyl-L-arginine (6 mg/min) reduced by 70% the vascular effects of L-arginine. In the whole population of 52 healthy subjects, there was an inverse correlation between age and blood pressure or platelet aggregation changes after L-arginine. Compared with matched controls (n = 20), the changes in mean blood pressure and platelet aggregation after L-arginine were significantly lower in non-insulin-dependent diabetic (n = 20) and hypercholesterolemic (n = 16), but not in hypertensive (n = 20), subjects. Changes in blood viscosity were significantly lower only in hypercholesterolemic subjects. Our findings suggest that an intravenous bolus of 3 g L-arginine may be a simple and useful tool to assess the endothelial control of blood pressure and platelet activity in health and disease.

Metabolic and cardiovascular effects of carvedilol and atenolol in non-insulin-dependent diabetes mellitus and hypertension. A randomized, controlled trial.

BACKGROUND: Diabetic patients are considered less suitable than nondiabetic patients for beta-blocker therapy because of the risk for worsened glucose and lipid metabolism and more severe hypoglycemic attacks. OBJECTIVE: To compare the metabolic and cardiovascular effects of carvedilol with those of atenolol in diabetic patients with hypertension. DESIGN: Randomized, double-blind, 24-week trial. SETTING: University hospital clinic. PATIENTS: 45 patients with non-insulin-dependent diabetes mellitus and hypertension. INTERVENTION: After a 4- to 6-week run-in period during which placebo was given in a single-blind manner, patients were randomly assigned to carvedilol or atenolol. MEASUREMENTS: An oral glucose tolerance test; assessment of insulin sensitivity and hormonal responses to insulin hypoglycemia; and assessment of lipid levels, blood pressure, left ventricular mass, and lipid peroxidation. RESULTS: Changes in systolic and diastolic blood pressure and left ventricular mass index were similar with carvedilol and atenolol (P > 0.2). Fasting plasma glucose and insulin levels decreased with carvedilol and increased with atenolol. Responses to carvedilol were greater than those to atenolol, as follows: increase in total glucose disposal, 9.54 mumol/kg of body weight per minute (95% CI, 7 to 11.9 mumol/kg per minute); decrease in plasma glucose response to oral glucose, 61 mmol/L x 180 minutes (CI, -101 to -21 mmol/L x 180 minutes); decrease in insulin response to oral glucose, 6.2 nmol/L x 180 minutes (CI, -9.8 to -2.6 nmol/L x 180 minutes); decrease in triglyceride level, 0.56 mmol/L (CI, -0.75 to -0.37 mmol/L; P < 0.001); increase in high-density lipoprotein cholesterol level, 0.13 mmol/L (CI, 0.09 to 0.17 mmol/L; P < 0.001); and decrease in lipid peroxidation, 0.25 mumol/L (CI, -0.34 to -0.16 mumol/L). CONCLUSIONS: By improving glucose and lipid metabolism and reducing lipid peroxidation, carvedilol may offer advantages in patients with diabetes and hypertension.

Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia.

BACKGROUND: Acute hyperglycemia may increase vascular tone in normal humans via a glutathione-sensitive, presumably free radical-mediated pathway. The objective of this study was to investigate whether or not the vascular effects of hyperglycemia are related to reduced availability of nitric oxide. METHODS AND RESULTS: Acute hyperglycemia (15 mmol/L, 270 mg/dL) was induced in 12 healthy subjects with an artificial pancreas. Systolic and diastolic blood pressures, heart rate, and plasma catecholamines showed significant increases (P < .05) starting after 30 minutes of hyperglycemia; leg blood flow decreased significantly (15%; P < .05) at 60 and 90 minutes. Platelet aggregation to ADP and blood viscosity also showed significant increments (P < .05). The infusion of L-arginine (n = 7, 1 g/min) but not D-arginine (n = 5, 1 g/min) or L-lysine (n = 5, 1 g/min) in the last 30 minutes of the hyperglycemic clamp completely reversed all hemodynamic and rheological changes brought about by hyperglycemia. Infusion of NG-monomethyl-L-arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis in 8 normal subjects produced vascular effects qualitatively similar to those of hyperglycemia but quantitatively higher (P < .05); however, heart rate and plasma catecholamine levels decreased during L-NMMA infusion, presumably as a consequence of baroreflex activation. Infusion of L-NMMA during hyperglycemia produced changes not different from those obtained during infusion of L-NMMA alone. CONCLUSIONS: The results show that acute hyperglycemia in normal subjects causes significant hemodynamic and rheological changes that are reversed by L-arginine. Moreover, the effects of hyperglycemia are mimicked to a large extent, but not entirely, by infusion of L-NMMA. This suggests that hyperglycemia may reduce nitric oxide availability in humans.

The vascular effects of L-Arginine in humans. The role of endogenous insulin.

This study aimed at evaluating whether increased availability of the natural precursor of nitric oxide, L-arginine, could influence systemic hemodynamic and rheologic parameters in humans and whether the effects of L-arginine are mediated by endogenous insulin. 10 healthy young subjects participated in the following studies: study I, infusion of L-arginine (1 g/min for 30 min); study II, infusion of L-arginine plus octreotide (25 microg as i.v. bolus + 0.5 microg/min) to block endogenous insulin and glucagon secretion, plus replacement of basal insulin and glucagon; study III, infusion of L-arginine plus octreotide plus basal glucagon plus an insulin infusion designed to mimic the insulin response of study I. L-Arginine infusion significantly reduced systolic (11+/-3, mean+/-SE) and diastolic (8+/-2 mmHg, P < 0.001) blood pressure, platelet aggregation (20+/-4%), and blood viscosity (1.6+/-0.2 centipois, P < 0.01), and increased leg blood flow (97+/-16 ml/min), heart rate, and plasma catecholamine levels (P < 0.01). In study II, plasma insulin levels remained suppressed at baseline; in this condition, the vascular responses to L-arginine were significantly reduced, except for plasma catecholamines which did not change significantly. In study III, the plasma insulin response to L-arginine was reestablished; this was associated with hemodynamic and rheologic changes following L-arginine not significantly different from those recorded in study I. These findings show that systemic infusion of L-arginine in healthy subjects induces vasodilation and inhibits platelet aggregation and blood viscosity. These effects are mediated, in part, by endogenous released insulin.

Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM patients.

OBJECTIVE: The endothelium plays a pivotal role in the regulation of vascular tone by releasing nitric oxide (NO). Increased availability of L-arginine, the natural precursor of NO, induces vasodilatation and inhibits platelet activity. We studied the effect of metformin on hemodynamic and rheological responses to L-arginine in patients with NIDDM. RESEARCH DESIGN AND METHODS: Ten newly diagnosed NIDDM patients with mild fasting hyperglycemia (7.5 +/- 0.3 mmol/l) and without evidence of both micro- and macrovascular complications were investigated. They received an intravenous infusion of L-arginine (1 g/min for 30 min) with evaluation of plasma glucose and insulin, systolic (sBP) and diastolic (dBP) blood pressure, heart rate and plasma catecholamines, platelet aggregation, and blood viscosity and filterability. The L-arginine test was repeated after an 8-week treatment with metformin (850 mg b.i.d.). RESULTS: Metformin treatment significantly reduced basal fasting plasma glucose, HbA1c, and platelet aggregation to ADP (P < 0.05); the other parameters did not change. During pretreatment test, L-arginine infusion decreased sBP (from 137 +/- 4.1 to 129 +/- 4.5 mmHg, P < 0.01) and dBP (from 79 +/- 1.9 to 75 +/- 1.2 mmHg, P < 0.01) without affecting heart rate or plasma catecholamines. Both platelet aggregation and blood viscosity showed significant decrements after L-arginine, while blood filterability did not change. After metformin treatment, the decrease in blood pressure after L-arginine infusion was significantly enhanced, with a maximal decrease of sBP of 12 +/- 3.4 mmHg (8 +/- 2.5 mmHg pretreatment, P < 0.05) and dBP of 9.5 +/- 2.4 mmHg (4.5 +/- 1.9 mmHg pretreatment, P < 0.01). Heart rate, plasma norepinephrine levels, and blood filterability also rose significantly (P < 0.05-0.01). The decrease in both platelet aggregation and blood viscosity after L-arginine was significantly amplified after metformin. CONCLUSIONS: We conclude that L-arginine infusion in newly diagnosed NIDDM patients without vascular complications produces relevant hemodynamic and theological changes, which are amplified by an 8-week treatment with metformin. Whether these vascular effects of metformin will improve the poor cardiovascular outlook of the diabetic patient is still unknown.

Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and reversal by antioxidants.

OBJECTIVE: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. DESIGN: Case-control study. SETTING: University hospital clinic. PATIENTS: 40 patients with diabetes and no evidence of cardiovascular complications and 40 controls matched for demographic variables and body habitus. INTERVENTIONS: Sublingual glyceryl trinitrate (0.3 mg) and transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for 7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to test the effects of antioxidant supplementation. MEASUREMENTS: Systolic, diastolic, and mean arterial pressure and heart rate; left ventricular ejection fraction; platelet aggregation, blood viscosity, and blood filterability in vitro and ex vivo. RESULTS: Compared with controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blood pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transdermal glyceryl trinitrate patches significantly reduced platelet aggregation (-38%; 95% CI, -49% to -27%) and blood viscosity (-8%; CI, -11% to -5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after administration of glyceryl trinitrate (both preparations). In patients with diabetes, glyceryl trinitrate paradoxically increased platelet aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynamic values did not change significantly. In both groups, rheologic responses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses to glyceryl trinitrate in patients with diabetes. CONCLUSIONS: Organic nitrates have beneficial effects on blood rheology in controls but not in patients with diabetes, in whom a paradoxical deterioration is seen. Antioxidant supplementation can normalize primary tolerance to the rheologic effects of nitrates in diabetes.

Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects.

The present study aimed at evaluating whether acute elevations of plasma glucose concentrations could influence systemic hemodynamic parameters and baroreflex activity in humans. Plasma glucose concentrations were acutely raised to 15 mmol/l in 12 healthy male volunteers. During hyperglycemia, there were significant increments of systolic [from 118 +/- 9 to 138 +/- 12 (SD) mmHg, P < 0.01] and diastolic (from 71 +/- 5 to 85 +/- 6 mmHg, P < 0.001) blood pressure, as well as heart rate (from 76 +/- 7 to 85 +/- 10 beats/min, P < 0.01) and plasma catecholamine levels. Both maximal and steady-state mean arterial pressure after squatting were higher during hyperglycemia (27 +/- 8 and 16 +/- 6 mmHg, respectively) compared with levels obtained during euglycemia (18 +/- 5 and 2 +/- 0.6 mmHg, respectively, P < 0.001). The infusion of the somatostatin analogue octreotide (25 micrograms as i.v. bolus followed by a 0.5 microgram/min infusion), to avoid the possible confounding vascular actions of insulin, did not influence the hemodynamic effects of hyperglycemia except for a lesser increase of both heart rate and plasma catecholamines. Glutathione (600 mg as an iv bolus followed by a 5 mg/min infusion) completely prevented the vascular effects of hyperglycemia. This study shows that acute hyperglycemia, similar to that observed in poorly controlled diabetic patients, produces relevant systemic hemodynamic changes and also alters baroreflex activity via a glutathione-sensitive presumably free radical-mediated pathway.

Tolrestat in the primary prevention of diabetic neuropathy.

OBJECTIVE: To compare the effects of tolrestat and placebo in patients with subclinical diabetic neuropathy. RESEARCH DESIGN AND METHODS: Non-insulin-dependent diabetes mellitus (NIDDM) patients with early involvement of the autonomic nervous system were identified by only one pathological (outside the 99% confidence interval of the normal population) squatting test (vagal or sympathetic). Fifty-seven patients entered a randomized, placebo-controlled, double-blind, parallel 52-week study of tolrestat at a dose of 200 mg/day. Cardiovascular reflex tests (squatting vagal and sympathetic tests, pressure gain, deep breathing, lying-to-standing, Valsalva maneuver, and orthostatic hypertension), vibration thresholds, tendon reflexes, and muscle strength were assessed throughout the study. RESULTS: At 12 months, nerve function significantly improved in patients receiving tolrestat and deteriorated in patients taking placebo. At baseline, the squatting vagal test was normal in 16 patients in the tolrestat group and in 15 patients in the placebo group. At 12 months, 25 patients taking tolrestat had a normalized squatting test, but only 6 patients taking placebo did (P = 0.02). Vibration perception threshold improved by a value of 6 +/- 3 V in the tolrestat group (P < 0.001) and deteriorated by a value of 3 +/- 1.8 V (P < 0.001) in the placebo group. CONCLUSIONS: Tolrestat may be useful in the primary prevention of diabetic neuropathy.

Medical hypothesis: cardiovascular complications of diabetes mellitus-from glucose to insulin and back.

Vascular complications such as atheroma, hypertension and macroangiopathy are the leading causes of morbidity and mortality in diabetic patients. Epidemiological and clinical data linking hyperinsulinaemia to both hypertension and atherosclerosis are inconsistent. Hyperglycaemia is the distinguishing feature of diabetes and it seems a likely candidate for the poor cardiovascular outlook of diabetic patients. High blood glucose levels cause selective impairment of endothelium-dependent relaxation and delay cell replication time of cultured human endothelial cells. These effects of hyperglycaemia are reversed by a number of antioxidants, including superoxide dismutase, catalase and glutathione. Impaired endothelium-dependent vasodilation has been reported both in Type 1 and Type 2 diabetic patient. The evidence for a role of oxygen-derived free radicals in the pathogenesis of vascular diabetic complications can be summarized as follows: 1) glucose can auto-oxidize generating oxygen derived free radicals; 2) elevated levels of oxygen derived free radicals are found in red blood cells, plasma and retina of diabetic animals and patients, and correlate with metabolic control; 3) endogenous antioxidants are all decreased in diabetic tissues and blood; and 4) treatment with different antioxidants may improve many of the metabolic abnormalities reported to occur in diabetic patients. The use of antioxidants to reduce the risk of coronary heart disease in diabetes should await the results of randomized trials with these drugs in the primary and secondary prevention of coronary disease.

Hyperinsulinemia in glucose intolerance: is it true?

To evaluate whether beta-cell hyperfunction characterizes glucose intolerant states per se independent of fasting glycemia, we conducted a case-control study among 430 subjects who were classified, by NDGG criteria, as having normal glucose tolerance (n = 230, 130M/130F), nondiagnostic tolerance (NDT, n = 100, 50M/50F) and impaired glucose tolerance (IGT, n = 100, 50M/50F). Thirty-four subjects (17M/17F) with normal glucose tolerance were matched by age, sex, body mass index (BMI), waist-to-hip ratio (WHR), fasting glucose and HbA1c with 30 NDT (15M/15F) and 30 IGT (15M/15F) subjects. The continuous and significant increase in insulin and C-peptide levels across categories of glucose tolerance (from normal to NDT to IGT) was no longer evident in the case-control study: at a fasting plasma glucose ranging from 5.2-5.5 mmol/L (HbA1c was 5%) the concentration of fasting C-peptide was 0.793 +/- 225 nmol/L (mean +/- SD) in subjects with normal glucose tolerance, 0.805 +/- 200 nmol/L in NDT and 0.807 +/- 231 nmol/L in IGT subjects (p = NS). Similarly, plasma concentrations of triglycerides and blood pressure values were similar when subjects of different categories were compared at the same level of glycemia. Sixteen normal subjects were rendered mildly hyperglycemic by a 24-h glucose infusion to match the fasting glucose level of NDT (1 mg/kg/min) and IGT (2 mg/kg/min) subjects. At the same fasting glucose level, normal subjects presented elevations of fasting C-peptide significantly (p < 0.01) higher than subjects belonging to the NDT and IGT categories.(ABSTRACT TRUNCATED AT 250 WORDS)

The squatting test. A useful tool to assess both parasympathetic and sympathetic involvement of the cardiovascular autonomic neuropathy in diabetes.

The heart rate responses observed after both squatting and standing are thought to be of reflex nature and may be useful to assess the functional integrity of parasympathetic and sympathetic nerves in diabetes. In the standard maneuver, each subject stood still for 3 min, then squatted down for 1 min, and at last stood up during an inspiratory phase. In 10 healthy subjects (25-31 years of age), lengthening of the R-R interval during squatting was abolished by atropine, whereas propranolol markedly attenuated shortening of the R-R interval at standing from squatting. Squatting test (SqT) ratios (SqT vagal [SqTv] = ratio between the R-R interval mean before squatting and the longest R-R interval after squatting; SqT sympathetic [SqTs] = ratio between the basal R-R interval and the shortest R-R interval at standing) were calculated in 558 healthy subjects and 346 diabetic patients (insulin-dependent diabetes mellitus/non-insulin-dependent diabetes mellitus: 103/243). Normal ranges (95 and 99% confidence intervals [CIs]) for subjects 20-74 years of age showed a statistically significant negative correlation with age. SqTv was outside the 99% CI in 145 (42%) diabetic patients and in 7 (1.3%) of the control subjects. The corresponding figures for SqTs were 40 and 0.8%, respectively. Age and duration of diabetes had a negative influence on SqT ratios. SqT ratios were compared with other reflex tests currently used for diagnosis of autonomic neuropathy: deep breathing (DB), lying-to-standing (LS), Valsalva manuever, and blood pressure change after standing (orthostatic hypotension [OH]).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of nitrendipine and cilazapril in patients with hypertension and non-insulin-dependent diabetes mellitus.

The metabolic and cardiovascular effects of nitrendipine and cilazapril in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20 NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg received a single-blind placebo for 4 weeks and then were randomized to receive 20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks according to a crossover, double-blind procedure. Nitrendipine and cilazapril reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and 19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels. Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure and LVMI levels and in increasing glucose disposal levels in these patients.