Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden.

Smoking has been linked with both increased and decreased risk of COVID-19, prompting the hypothesis of a protective role of nicotine in the pathogenesis of the disease. Studies of the association between use of smokeless tobacco and COVID-19 would help refining this hypothesis. We analysed data from 424,386 residents in the Stockholm Region, Sweden, with information on smoking and smokeless tobacco (snus) use prior to the pandemic obtained from dental records. Diagnoses of COVID-19 between February and October 2020 were obtained from health-care registers. We estimated the risk of receiving a diagnosis of COVID-19 for current smokers and for current snus users relative to non-users of tobacco, adjusting for potential confounders (aRR). The aRR of COVID -19 was elevated for current snus users (1.09 ;95%CI = 0.99-1.21 among men and 1.15; 95%CI = 1.00-1.33 among women). The risk for women consuming more than 1 can/day was twice as high as among non-users of tobacco. Current smoking was negatively associated with risk of COVID-19 (aRR = 0.68; 95% CI = 0.61-0.75); including hospital admission (aRR = 0.60; 95% CI = 0.47-0.76) and intensive care (aRR = 0.43; 95% CI = 0.21-0.89). The hypothesis of a protective effect of tobacco nicotine on COVID-19 was not supported by the findings. The negative association between smoking and COVID-19 remains unexplained.

Inhibitory function of secretory leukocyte proteinase inhibitor (SLPI) in human saliva is HIV-1 specific and varies with virus tropism.

OBJECTIVE: Secretory leukocyte proteinase inhibitor (SLPI) is an endogenous mucosa associated protein that has been proposed to possess anti-human immunodeficiency virus type 1 (HIV-1) activity. The aim of this study was to investigate the biological function of SLPI in salivary mediated inhibition of HIV infection and in addition the inhibitory effect of SLPI using isolates of varied virus tropism. MATERIAL AND METHODS: The inhibitory effect of HIV-1 infection in vitro, mediated by 60 different saliva samples was analyzed with respect to levels of SLPI. Salivary samples depleted from IgA and SLPI, respectively, were further analyzed for anti-HIV activity. The antiviral effect of recombinant SLPI was investigated within an in vitro system of HIV-1 infection of target cells using a panel of viral isolates with distinct coreceptor usage. Furthermore we tested a panel of overlapping synthetic peptides, representing the amino acids in SLPI, for their capacity to inhibit HIV-1 infection of human peripheral blood mononuclear cells (PBMCs). RESULTS AND CONCLUSIONS: These experiments show that elevated levels of salivary SLPI can be associated with an increased inhibitory effect of the whole saliva sample, and that this inhibitory effect is decreased with broad coreceptor usage of the virus.

Normal responses of atrial natriuretic factor and renal tubular function to sodium loading in hypertension-prone humans.

BACKGROUND: In order to explore the hypothesis of an atrial natriuretic factor (ANF) deficiency in prehypertension, we compared the response to sodium loading on ANF and renal function in subjects with positive and negative histories of hypertension. METHODS: Twenty-two offspring of hypertensive parents (OH) and 20 offspring of normotensive parents (ON) were studied after 4 days of low (50 mmol/day) or high (300 mmol/day) dietary sodium intake. The diets were allocated randomly. Blood pressure (BP), renal function, plasma concentration of ANF, cyclic guanosine monophosphate (cGMP), renin, angiotensin I and II, aldosterone, endothelin and catecholamines were determined during a clearance period of 90 min on both diets. Neurohormones were measured by radioimmunoassays. Renal function was determined by simultaneous measurements of 51Cr-ethylenediaminetetraacetate (a marker of glomerular filtration rate), lithium and sodium clearances. RESULTS: Supine systolic and diastolic BPs were significantly elevated in OH, with both low and high dietary sodium intake. There was no difference in ANF and cGMP concentrations on the low sodium diet. Increasing sodium intake caused a similar increase in ANF in OH and ON but cGMP did not change significantly. As expected the activity of the renin-angiotensin-aldosterone system was decreased by enhancing sodium intake but with both low and high sodium intake plasma renin concentration was significantly higher in OH than in ON. Activation of the sympathetic nervous system with low sodium intake was indicated by a moderate increase in plasma concentrations of epinephrine and norepinephrine in both groups. The renal effects were characterized by significant increases in GFR, lithium and sodium clearances with increasing sodium intake. There were no differences between OH and ON. Estimated values of fractional proximal and distal tubular sodium reabsorption decreased significantly and in a similar way in both OH and ON. CONCLUSION: These results indicate that the renal and neuroendocrine responses to dietary sodium loading are similar in both OH and ON. The only difference was a higher BP and an elevated plasma renin concentration on both dietary regimens in OH compared with ON. In particular, in OH and ON an identical increase in plasma ANF concentration in response to sodium loading was found. Thus, this study cannot support the hypothesis of a dysregulation of ANF in hypertension-prone humans.

Hyperglycaemia enhances renal magnesium excretion in type 1 diabetic patients.

Magnesium depletion is a common feature of diabetes mellitus, apparently related to glycaemic control. The aim of the study was to investigate the isolated effect of hyperglycaemia upon renal magnesium excretion. Urinary magnesium excretion rates were measured in 10 patients with Type 1 diabetes mellitus on two different days with different levels of blood glucose concentration but equal plasma insulin concentration. On a hyperglycaemic day, an i.v. infusion of 20% glucose was started at the end of a euglycaemic baseline period, increasing blood glucose concentration from 5.3 mmol/L to 12.3 mmol/L. There was no major glucosuria. On the hyperglycaemic day the renal magnesium excretion and clearance were raised by a factor of 2.4 compared to the euglycaemic day. Plasma magnesium concentration decreased 3% during hyperglycaemia. In conclusion, blood glucose excursions influence magnesium homeostasis independently of insulin levels in Type 1 diabetic patients. This effect is primarily due to an increased renal magnesium clearance during hyperglycaemia.

Renal effects of hyperinsulinaemia in subjects with two hypertensive parents.

The aim of this investigation was to study the effects of isoglycaemic hyperinsulinaemia on the renal metabolism of electrolytes and water in subjects with a strong genetic predisposition to essential hypertension, compared with that in non-predisposed subjects. We studied 25 normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 22 age- and sex-matched subjects whose parents were both normotensive. Diabetes or morbid obesity in any subject or parent excluded the family. The 24-h blood pressure was measured. The subjects received an isocaloric diet with a fixed content of sodium and potassium for 4 days before the study. An isoglycaemic, hyperinsulinaemic clamp with infusion of insulin (40 munits.min(-1).m(-2)) was performed. We measured the renal clearance of diethylenetriaminepenta-acetic acid, sodium, potassium and lithium both under basal conditions and during hyperinsulinaemia. In response to hyperinsulinaemia, renal sodium clearance decreased to a significantly greater extent in the hypertension-prone subjects [0.57 (0.74, 0.36) ml.min(-1).1.73 m(2) (median and quartiles)] than in the controls [0.34 (0.56, 0.18) ml. min(-1).1.73 m(2)] (P=0.04). Compared with the controls, the subjects predisposed to hypertension had a higher 24-h diastolic blood pressure [78 (70, 82) mmHg, compared with 73 (68, 77) mmHg], but a similar insulin sensitivity index ¿10(7)x[313 (225, 427)] compared with 10(7)x[354 (218, 435)] l(2).min(-1).pmol(-1).kg(-1)¿. Thus the sodium-retaining effect of insulin was more pronounced in subjects with a strong genetic predisposition to essential hypertension than in subjects with normotensive parents. This effect may contribute to the development of hypertension in subjects with a genetic predisposition to hypertension.

Insulin resistance, exercise capacity and body composition in subjects with two hypertensive parents.

OBJECTIVE: To study insulin resistance in subjects with strong genetic predisposition to essential hypertension, compared with non-disposed subjects. SUBJECTS: Thirty normotensive subjects aged 18-35 years whose parents both had essential hypertension, and 30 age- and sex matched subjects whose parents were both normotensive, were studied. Subjects or parents with diabetes and morbid obesity were excluded. METHODS: The study comprised (1) a frequent sampling oral glucose tolerance test; (2) an isoglycemic hyperinsulinemic clamp study; (3) an analysis of body composition by dual-energy X-ray absorptiometry; (4) an exercise test with gas exchange analysis; and (5) investigation of composition of usual diet by diet registration for 5 days. RESULTS: The 24-h diastolic blood pressure was higher in subjects predisposed to hypertension compared with the controls: 78.1 versus 74.0 mmHg (confidence interval for the difference between the means; -0.5; -7.9), but the insulin sensitivity index was similar: 312 versus 362 I(2) min(-1) pmol(-1) kg(-1) (28; -129). The two groups were similar in terms of body composition, exercise capacity and composition of usual diet. Resting and 24-h diastolic blood pressures were correlated to abdominal fat mass but not to insulin sensitivity. CONCLUSION: Subjects with a strong genetic predisposition to essential hypertension had increased diastolic blood pressure compared with subjects with normotensive parents, but they were not insulin resistant. This may be due to the subjects being highly selected as to confounding factors. The increased blood pressure in the hypertension prone subjects could not be attributed to differences in body composition, exercise capacity or dietary habits.

Salivary sIgA response in HIV-1 infection.

Local and systemic production of total and HIV-1 specific IgA was determined in whole saliva and serum from 45 HIV-1-infected individuals and 15 healthy controls. The antigenic domains important for sIgA and IgG binding, respectively, was investigated with epitope mapping using synthetic peptides of HIV-1 proteins. Decreased levels of total sIgA in saliva were found among patients with low CD4+ cell counts in advanced stages of acquired immunodeficiency. HIV-1 specific IgA response, predominantly directed to the envelope proteins, was found in saliva and serum also at later stages of disease. Analyses using peptide enzyme-linked immunosorbent assays (ELISA) showed that the sIgA antibody response in saliva was mainly directed to the V4 region (aa 385-409) and a more C-terminal part of the V3-region (aa 325-344) compared with the IgG response, which predominantly was directed to a more central part of the V3 loop (aa 308-325). A similar picture was seen for immunoglobulins of the two isotypes derived from serum. We have in this study shown IgA epitope-specific immune response within HIV-1 gp160, indicating that antibodies of IgA isotype may recognize somewhat different antigenic domains compared to IgG antibodies.

Characterization of neutralizing sites in the second variable and fourth variable region in gp125 and a conserved region in gp36 of human immunodeficiency virus type 2.

Several determinants of human immunodeficiency virus (HIV) have been suggested to harbor sites important for neutralization. The third variable region (V3) of the envelope glycoprotein (gp) is an important neutralizing determinant for both serotypes of HIV. The localization of additional neutralizing regions is an urgent task because the virus appears to mutate to phenotypes that escape neutralizing antibodies. Therefore, we have focused on the possibility of finding other immunodominant regions in the envelope glycoproteins of human immunodeficiency virus type 2 (HIV-2). By immunization of guinea pigs with peptides corresponding to different selected regions of gp125 and gp36, we have found three antigenic determinants located in the V2 and V4 regions of the envelope protein gp125, and one region in the glycoprotein gp36, which are important for human antibody binding and also as targets for neutralization. The peptide representing the V2 region had the most pronounced capacity to induce neutralizing anti-HIV-2 antibodies in guinea pigs. Neutralizing activity was also detected in an antipeptide guinea pig sera representing a linear site in gp36, amino acids 644-658. A substitution set of peptides representing the conserved antigenic site in the central part of gp36 was used to identify the role of individual amino acids important for human antibody binding.

Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.

The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.

[Salt--an analysis of the connection between intake and health]. / Salt--en analyse af sammenhaenge mellem indtag og helbredstilstand.

The average salt intake (sodium chloride) in Denmark is about 10 g/person/day, which is approximately 8 times higher than the estimated need. Salt added during industrial processing of foods constitutes more than 50% of the daily salt intake. Observational and experimental epidemiological studies indicate no decisive effects on blood pressure in humans caused by considerable variations in the daily salt intake. However, a small group of patients with hypertension may lower their blood pressure by reducing the daily intake of salt to 5 g. It has not been convincingly documented that high salt intake is an independent risk factor in the pathogenesis of asthma, osteoporosis, toxaemia of pregnancy or apoplectic stroke. On the other hand, several epidemiological studies point to the fact that the intake of salted foods may increase the risk of gastric cancer. It is recommended 1) that the food industry as far as possible limits the addition of salt, 2) that foods are supplied with a declaration of the salt content, and 3) that the research in this field is strengthened to facilitate the identification of persons at increased risk of developing disorders associated with high salt intake.

Insulin increases renal magnesium excretion: a possible cause of magnesium depletion in hyperinsulinaemic states.

The effects of insulin upon renal magnesium excretion were examined. Urinary magnesium excretion rates were measured in seven healthy volunteers (three men, four women) before and during a euglycaemic, hyperinsulinaemic clamp. Insulin was infused at 120 pmol m-2 min-1 and at 240 pmol m-2 min-1. Compared to baseline, the renal magnesium excretion increased 30% during the infusion of insulin at a rate of 120 pmol m-2 min-1. During infusion of insulin, 240 pmol m-2 min-1, renal magnesium excretion increased 50% compared to baseline. There were no changes in either glomerular filtration rates, plasma magnesium, urinary volume or general changes in the renal handling of divalent ions as judged by an unchanged urinary excretion rate of calcium (0% during infusion of insulin, 120 pmol m-2 min-1, and 8% increase during infusion of 240 pmol m-2 min-1 (NS). During the 120 pmol m-2 min-1 insulin infusion rate, plasma insulin rose from 46.1 pmol I-1 to 158.8 pmol I-1 and during the 240 pmol m-2 min-1 insulin infusion rate, mean plasma insulin concentration was 361.4 pmol I-1. Thus, physiological concentrations of insulin induce a specific increase in the renal excretion of magnesium. This might partly explain the magnesium depletion observed in various hyperinsulinaemic states, diabetes mellitus, atherosclerosis, hypertension, and obesity.

Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X.

Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic, hyperinsulinemic clamp was performed in combination with indirect calorimetry. Biopsy of vastus lateralis muscle was taken in the basal state and after 4 hours of euglycemia and hyperinsulinemia (2 mU.kg-1.min-1). The fasting level of "true" serum insulin was significantly higher (43 +/- 6 v 22 +/- 3 pmol/L, P < .02) and the rate of insulin-stimulated glucose disposal to peripheral tissues was lower in patients with MA (13.4 +/- 1.0 v 18.2 +/- 1.4 mg.kg fat-free mass [FFM]-1.min-1, P < .02) due to a decrease in nonoxidative glucose metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P < .02). No difference was found in glucose or lipid oxidation rates between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.

Diabetic nephropathy is characterized by hypertension and a relentless decline in kidney function. Angiotensin-converting enzyme inhibitors have been claimed to preserve kidney function better than an equal blood pressure (BP) reduction with conventional antihypertensive treatment (renoprotection). We compared the effect on kidney function of lisinopril (10-20 mg/day) and atenolol (50-100 mg/day) in hypertensive NIDDM patients (mean age 60 +/- 8 years) with diabetic nephropathy. Forty-three (21 lisinopril and 22 atenolol) patients were enrolled in a 1-year randomized double-blind parallel study. Eight patients dropped out, and the results for the remaining 35 patients (16 lisinopril and 19 atenolol) are presented. Diuretics were required in 10 of 16 lisinopril patients and 12 of 19 atenolol patients. The following variables were measured: 24-hour ambulatory BP (Takeda TM2420), albuminuria (enzyme-linked immunosorbent assay), fractional albumin clearance, and glomerular filtration rate (GFR) ([51Cr]EDTA technique). The average reduction in mean arterial BP during the 12 months was identical in the two groups 12 +/- 2 vs. 11 +/- 1 mmHg in the lisinopril and atenolol group, respectively. Albuminuria was on average reduced 45% in the lisinopril group vs. 12% in the atenolol group (P < 0.01), and fractional albumin clearance was on average reduced 49% in the lisinopril group vs. 1% in the atenolol group (P < 0.05). GFR declined identically in the two groups 11.7 +/- 2.3 vs. 11.6 +/- 2.3 ml.min-1.year-1 in the lisinopril and atenolol groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Lithium clearance in the evaluation of segmental renal tubular reabsorption of sodium and water in diabetes mellitus.

Lithium is the best available marker of proximal tubular reabsorption of fluid. The first part of the present thesis reviews the background for the use of the lithium clearance (CLi) method. Micropuncture studies on proximal reabsorption of lithium, showed that CLi is a reasonably correct measure of end-proximal fluid delivery rate, even during osmotic diuresis. During severe salt restriction, distal reabsorption of lithium renders the CLi method inappropriate in animals, but this problem does probably not occur in humans. The major current issue is whether a quantitatively significant reabsorption of lithium occurs in the loop of Henle. Available evidence is in accord with the interpretation that it does not occur. The interpretation of results form CLi studies depends to a surprising degree on the investigators beliefs about renal physiology. In the evaluation of proximal tubular function, the relevant parameter is the absolute proximal reabsorption rate of fluid and sodium. In the evaluation of integrated distal tubular reabsorption of sodium, the relevant parameter is the fractional distal reabsorption rate of sodium. The fractional CLi does not give meaningful information, and calculated absolute distal reabsorption rate of sodium is inherently not suited to detect modest changes in distal reabsorption leading to large changes in sodium excretion. Results from the use of the CLi method in relation to diabetes are reviewed in the second section. Even in IDDM patients with early diabetic nephropathy, the proximal reabsorption rate is elevated, resulting in a normal CLi despite glomerular hyperfiltration. Overnight euglycemia did not change GFR in IDDM patients, but during maintained euglycemia, GFR was normalized. A few hours of hyperglycemia prevented the decline in GFR, whereas CLi was unchanged. Thus hyperglycemia produced changes in renal function similar to those observed previously, but the time-course of the effect of euglycemia on kidney function is delayed. Plasma levels of atrial natriuretic peptide, renin and glucagon were not importantly affected by plasma glucose. In NIDDM patients CLi was normal, despite slight hyperfiltration, although this observation must be confirmed in a study with larger sample size. Prompted by the clinical observation of a marked decline in the GFR induced by carbonic anhydrase inhibitors, we studied the renal effects of acetazolamide in a controlled study.(ABSTRACT TRUNCATED AT 400 WORDS)

Glucose-fatty acid cycle operates in humans at the levels of both whole body and skeletal muscle during low and high physiological plasma insulin concentrations.

Plasma non-esterified fatty acid concentrations were elevated acutely (Intralipid+heparin infusion) in 14 normal humans in order to study the effects of fatty acids on whole-body basal and insulin-stimulated glucose metabolism, and on activities of skeletal muscle key enzymes. Whole-body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated (3 h, 40 mU.m-2.min-1) steady-state periods. Total peripheral glucose uptake was unaffected by Intralipid infusion in the basal state, whereas it decreased during Intralipid infusion in the hyperinsulinemic state (10.7 +/- 0.7 vs 8.7 +/- 0.8 mg.kg-1 fat-free mass.min-1, p < 0.02). Intralipid infusion decreased whole-body glucose oxidation in the basal state (1.3 +/- 0.2 vs 0.8 +/- 0.1 mg.kg-1 fat-free mass.min-1, p < 0.001) and during hyperinsulinemia (3.6 +/- 0.2 vs 1.7 +/- 0.2 mg.kg-1 fat-free mass.min-1 p < 0.001). Whole-body nonoxidative glucose uptake increased during Intralipid infusion in the basal state and was unaffected in the hyperinsulinemic state. The skeletal muscle pyruvate dehydrogenase activity ratio decreased in the basal state during Intralipid infusion (55 +/- 6 vs 43 +/- 5%, p < 0.05), whereas no statistical significant decrease in the pyruvate dehydrogenase activity ratio was observed during insulin infusion (57 +/- 8 vs 47 +/- 5%, NS). Insulin increased the activity of the active form of pyruvate dehydrogenase on the control day, but not during Intralipid infusion. Activities of phosphofructokinase and glycogen synthase were unaffected by Intralipid infusion. Plasma glucose concentrations were similar during Intralipid infusion and on the control day, whereas Intralipid infusion increased the muscle glucose content in the basal state (1.36 +/- 0.09 vs 1.77 +/- 0.12 mmol/kg dry wt, p < 0.05) and in the hyperinsulinemic state (1.23 +/- 0.09 vs 1.82 +/- 0.16 mmol/kg dry wt, p < 0.05). Insulin increased the muscle lactate content on the control day (6.50 +/- 0.95 vs 8.65 +/- 0.77 mmol/kg dry wt, p < 0.05), but not during Intralipid infusion. In conclusion, the glucose-fatty acid cycle operates in humans in vivo at the levels of both whole body and skeletal muscle during both low and high physiological insulin concentrations.

Effect of hyperglycemia per se on glucose turnover rates in patients with insulin-dependent diabetes.

The effect of hyperglycemia, per se, on glucose utilization and hepatic glucose production was reevaluated in eight C-peptide-negative insulin-dependent diabetic patients using primed-continuous noncontaminated 3-3H-glucose infusion and labeled glucose infusates. The night before study, euglycemia was maintained by a variable insulin infusion. During the studies, insulin was infused at basal replacement rates determined as the rate required to maintain euglycemia in the morning. After a 2-hour equilibration period, either plasma glucose level was increased to 12 mmol/L for 4 hours using a variable glucose infusion, or no glucose was infused (control day). On the hyperglycemic day, glucose utilization increased 16% (86 +/- 2 to 99 +/- 4 mg.m-2.min-1, P < .02) and glucose production decreased 45% (85 +/- 3 to 47 +/- 4 mg.m-2.min-1, P < .01). On the control day, both glucose utilization and glucose production decreased (84 +/- 3 to 68 +/- 3 and 84 +/- 3 to 65 +/- 3 mg.m-2.min-1, respectively; both P < .01). Therefore, comparing rates at the end of the hyperglycemic and control studies, glucose utilization was increased by 45% and glucose production was decreased by 28% in response to hyperglycemia (both P < .01). Thus hyperglycemia, at basal insulin levels enhanced glucose utilization and suppressed glucose production in insulin-dependent diabetic patients. Quantitatively, the enhancement of glucose utilization was more important than the suppressive effect on glucose production.

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension.

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril, 50 to 100 mg metoprolol, 12.5 to 25 mg hydrochlorothiazide, and placebo, each given twice daily for 8 weeks. Antidiabetic treatment remained unchanged during the study. After receiving placebo for a 4 week run-in period, arterial blood pressure was 168/101 +/- 93/10 (mean +/- SEM) mm Hg. Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 +/- 2 mm Hg: captopril, 92 +/- 1 mm Hg; metoprolol, 90 +/- 1 mm Hg; hydrochlorothiazide, 91 +/- 1 mm Hg. Metabolic variables were not significantly altered by captopril and metoprolol, while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 +/- 0.3 to 8.2 +/- 0.4% (P less than .001), decreased high-density lipoprotein-cholesterol from 1.19 +/- 0.08 to 1.10 +/- 0.06 mmol/L (P less than .05). Glomerular filtration rate, urinary albumin excretion, orthostatic blood pressure response, and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods. The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo. We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function, while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile.

Prevalence and causes of albuminuria in non-insulin-dependent diabetic patients.

A prospective study of the prevalence and causes of persistent albuminuria (greater than 300 mg/24 hr) was conducted in non-insulin-dependent diabetic (NIDDM) patients, age less than 66 years, attending a diabetic clinic during 1987. All eligible patients (N = 370) were asked to collect at least one 24-hour urine sample for albumin analysis. Urine collection was obtained in 224 males and 139 females (98%). Fifty patients (7 women) suffered from persistent albuminuria (13.8%). The prevalence of albuminuria was significantly higher in males (19%) than in females (5%). A kidney biopsy was performed in 35 patients (70%). The kidney biopsies revealed diffuse and/or nodular diabetic glomerulosclerosis in 27 patients (77%), while the remaining eight patients (23%) had a variety of non-diabetic glomerulopathies, such as minimal lesion and mesangioproliferative glomerulonephritis. Diabetic retinopathy was present in 15 of 27 patients (56%) with diabetic glomerulosclerosis, while none of the eight patients with a non-diabetic glomerulopathy had retinopathy. Our cross sectional study has revealed a high prevalence of albuminuria and of non-diabetic glomerulopathy as a cause of this complication in NIDDM patients. Presence of diabetic retinopathy strongly suggests that a diabetic glomerulopathy is the cause of albuminuria. Albuminuric non-insulin-dependent diabetic patients without retinopathy require further evaluation, that is, kidney biopsy.

Effect of acute hyperglycemia on glucose metabolism in skeletal muscles in IDDM patients.

The effect of acute hyperglycemia on glucose metabolism in skeletal muscles was assessed during replacement insulin infusion in 11 patients with insulin-dependent diabetes mellitus (IDDM). With a primed continuous [3-3H]glucose infusion and indirect calorimetry, glucose metabolism was assessed during a basal period (plasma glucose [PG] 5 mM) and during a hyperglycemic period (4-h i.v. glucose infusion, PG 12.1 mM). Biopsies were taken from the vastus lateralis muscle during both periods. On a control day, glucose metabolism was assessed in 10 patients during a basal period (PG 5.2 mM) and after 4 h with no glucose infusion (PG 4.2 mM). Nonoxidative glucose disposal increased during hyperglycemia (32 +/- 7 vs. 51 +/- 9 mg.m-2.min-1, P less than 0.05), whereas glucose oxidation remained constant. On the control day, nonoxidative glucose disposal decreased from the basal to the second (control) period (33 +/- 7 vs. 22 +/- 6 mg.m-2.min-1, P less than 0.05), and glucose oxidation remained constant. The activity of glycogen synthase in muscle biopsies (fractional velocities [0.1 and 10 mM glucose 6-phosphate (G6P)]) decreased slightly during hyperglycemia (18 +/- 2 vs. 12 +/- 2%, P less than 0.05) and on the control day (26 +/- 4 vs. 20 +/- 3%, P less than 0.05). Hyperglycemia increased the intracellular concentration of free glucose, corrected for estimated extracellular glucose (0.56 +/- 0.11 vs. 1.43 +/- 0.19 mM, P less than 0.01), G6P (0.14 +/- 0.04 vs. 0.23 +/- 0.08 mM, P less than 0.02), and lactate (2.88 +/- 0.33 vs. 4.46 +/- 0.61 mM, P less than 0.05), whereas these substrate concentrations remained constant on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)