Lipids and glucose in type 2 diabetes: what about the beta-cell and the mitochondria?: response to Boden and Laakso.
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Blood Glucose↗
Biomedical subjects
Itamar Raz
Publications and source records attributed to Itamar Raz.
Dose-response relationship of oral insulin spray in healthy subjects.
OBJECTIVE: To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin. RESEARCH DESIGN AND METHODS: In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin. RESULTS: The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 +/- 9 vs. 145.7 +/- 49.5 min, P < 0.05). Maximum serum insulin levels (C(max)) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 +/- 19.6 vs. 34.0 +/- 7.4 microU/ml, NS). The Ins-AUC(0-120) (area under the curve from 0 to 120 min for serum insulin) (339.8 +/- 218, 681.3 +/- 407, and 1,586.7 +/- 8 microU/ml, P < 0.05) and C(max) (7.6 +/- 2.8, 16.4 +/- 9.3, and 39.1 +/- 19.6 microU/ml, P < 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 +/- 12 vs. 77.8 +/- 3 min, P < 0.05), earlier peak (44.2 +/- 10 vs. 159.2 +/- 68 min, P < 0.05), and a shorter duration of action (85.1 +/- 25 vs. 319.2 +/- 45 min, P < 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 +/- 1.0, 3.09 +/- 1.7, and 4.6 +/- 1.5 mg . kg(-1) . min(-1), P < 0.05) and the GIR-AUC(0-120) (amount of glucose infused from 0 to 120 min) (106.7 +/- 74.3, 162.9 +/- 116.1, and 254 +/- 123 mg/kg) increased in a dose-dependent relationship for the three doses. CONCLUSIONS: Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted.
Administration, Oral↗
Clinical, socioeconomic, and lifestyle parameters associated with erectile dysfunction among diabetic men.
OBJECTIVE: Erectile dysfunction is frequently observed in diabetes. The current study aims to assess the association of a comprehensive set of clinical, socioeconomic, and lifestyle parameters with erectile dysfunction in diabetic men. RESEARCH DESIGN AND METHODS: Participants were randomly selected from male patients (age >18 years) treated in 26 diabetes clinics in Israel. Participants completed a self-reported questionnaire on demographic, socioeconomic, and lifestyle characteristics and on erectile function, using the IIEF-15 (International Index of Erectile Function). Information on diabetes type, duration, treatment, and control; microvascular complications and cardiovascular disease; drug therapy; blood pressure; and lipid levels was also obtained. RESULTS: Information on erectile function was obtained in 1,040 patients. Their mean age was 57 years, and their median diabetes duration was 8 years (range <1-50). Normal erectile function was found in 13.5% of the patients and severe erectile dysfunction in 30.1%. The characteristics found to be significantly associated with erectile dysfunction [associations presented as adjusted odds ratio (95% CI)] were: patient's age (5-year increments): 1.38 (1.29-1.48); diabetes duration (5-year increments): 1.16 (1.07-1.26); current HbA(1c) level (1% increment): 1.10 (1.01-1.19); any microvascular disease: 1.43 (1.09-1.88); cardiovascular disease: 1.78 (1.27-2.48); and diuretic treatment: 1.78 (1.09-2.91). Leisure time and work-related physical activity and consumption of small amounts of alcohol were found to be protective: 0.51 (0.36-0.72) and 0.70 (0.51-0.97), respectively. CONCLUSIONS: In diabetic men, erectile dysfunction severity increases with age and diabetes duration, poor glycemic control, presence of microvascular complications, diuretic treatment, and cardiovascular disease. Physical activity and alcohol intake may be protective. These findings can guide clinicians in taking preventive measures and undertaking early screening and treatment in high-risk patients.
Adult↗
High frequency of pre-diabetes, undiagnosed diabetes and metabolic syndrome among overweight Arabs in Israel.
BACKGROUND: Increased insulin resistance, which is associated with obesity, is believed to underlie the development of metabolic syndrome. It is also known to increase the risk for the development of glucose intolerance and type 2 diabetes. Both conditions are recognized as causing a high rate of cardiovascular morbidity and mortality. OBJECTIVES: To assess the prevalence of metabolic syndrome and different glucose intolerance states in healthy, overweight Arab individuals attending a primary healthcare clinic in Israel. METHODS: We randomly recruited 95 subjects attending a primary healthcare clinic who were healthy, overweight (body mass index > 27) and above the age of 40. Medical and family history was obtained and anthropometric parameters were measured. Blood chemistry and oral glucose tolerance test were performed after overnight fasting. RESULTS: Twenty-seven percent of the subjects tested had undiagnosed type 2 diabetes according to WHO criteria, 42% had impaired fasting glucose and/or impaired glucose tolerance and only 31% had a normal OGTT. Metabolic syndrome was found in 48% according to criteria of the U.S. National Cholesterol Education Program, with direct correlation of this condition with BMI and insulin resistance calculated by homeostasis model assessment. Subjects with metabolic syndrome had a higher risk for abnormality in glucose metabolism, and the more metabolic syndrome components the subject had the higher was the risk for abnormal glucose metabolism. Metabolic syndrome predicted the result of OGTT with 0.67 sensitivity and 0.78 specificity. When combined with IFG, sensitivity was 0.83 and specificity 0.86 for predicting the OGTT result. CONCLUSIONS: According to our initial evaluation approximately 70% of the overweight Arab population in Israel has either metabolic syndrome or abnormal glucose metabolism, indicating that they are at high risk to develop type 2 diabetes and cardiovascular morbidity and mortality. This population is likely to benefit from an intervention program.
Arabs↗
Complex impact of obesity on type 2 diabetes.
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Adolescent↗
Tongue necrosis and pericarditis.
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Adult↗
Increased expression of endothelin-converting enzyme-1c isoform in response to high glucose levels in endothelial cells.
Endothelin-1 (ET-1) is both a potent vasoconstrictor and mitogenic factor that has been implicated as a cause of the micro- and macrovascular complications of diabetes mellitus. The pathway by which the high-glucose environment of diabetes mediates increased levels of endothelins has not been completely elucidated but appears to involve endothelin-converting enzyme (ECE-1), which converts inactive big ET-1 to active ET-1 peptide. To determine the effect of high glucose concentrations on the expression of ECE-1, hybrid endothelial cells (EA.hy926) and human umbilical vein endothelial cells (HUVEC) were both grown in various glucose concentrations. There was a 2-fold increase in ECE-1 immunoreactivity in the EA.hy926 cell line growing in medium containing 22.2 versus 5.5 mmol/l glucose after 24 h, which rose to greater than 20-fold after 5 days. Similar results were seen with HUVEC. Bradykinin or NG-nitro-L-arginine methyl ester did not change the effect of high glucose on ECE-1 protein expression. High glucose induced a 72 and 41% increase in total protein kinase C (PKC) activity in both EA.hy926 cells and HUVEC, respectively, and a 39, 49 and 109% elevation in PKC beta1, beta2 and delta expression, respectively, in EA.hy926 cells. The increase in ECE-1 expression was inhibited in both cell cultures by GF109203X (5 micromol/l), a general PKC inhibitor, while addition of 10 nmol/l phorbol myristic acid to EA.hy926 cells or HUVEC growing on medium containing 5.5 mmol/l glucose increased ECE-1 expression to a level similar to that of cells conditioned in high glucose. Human ECE-1 protein exists in four different isoforms, termed 1a, 1b, 1c and 1d. Northern blot analysis revealed that only ECE-1c isoform mRNA levels increased. Immunohistochemical staining of EA.hy926 cells grown in high glucose concentrations demonstrated an increase in the ECE-1c isoform, which occurred mainly in the plasma membrane. These results showed that the PKC pathway may play an important role in the glucose-mediated induction of ECE-1 expression. The main isoform to increase in response to high glucose was ECE-1c. This enzyme may be one of the factors contributing to the elevated ET-1 peptide levels observed in diabetes.
Aspartic Acid Endopeptidases↗
Comparison of pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and subcutaneous insulin injection in healthy subjects using the euglycemic clamp technique.
BACKGROUND: Oral insulin spray is a new, noninjectable method of insulin delivery. This system delivers an aerosol of uniform-sized droplets containing regular human insulin at a high velocity into the oropharyngeal cavity for local transmucosal absorption. OBJECTIVE: The purpose of this study was to compare the pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and SC insulin injection in healthy subjects. METHODS: Healthy male volunteers aged 21 to 25 years participated in this open-label study conducted at the Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel. Subjects presented at 2 visits separated by 7 to 14 days. At both visits, the euglycemic clamp technique was used to maintain a constant blood glucose level. At one visit, subjects received regular human insulin 0.1 U/kg by SC injection. At the other visit, subjects received 15 puffs (150 U) of oral insulin spray. The pharmacokinetic (insulin absorption) and pharmacodynamic (glucose uptake) properties of the drugs were evaluated using blood analyses over the subsequent 360 minutes. RESULTS: Six volunteers were enrolled (mean [SD] age, 22.8 [1.2] years; mean [SD] body mass index, 23.2 [2.2] kg/m(2)). The mean (SD) baseline-corrected C(max) was significantly higher with oral insulin spray compared with SC insulin (54.0 [20.3] vs 30.8 [6.1] microU/mL; P = 0.028). Mean (SD) T(max) was significantly shorter with oral insulin spray compared with SC insulin (23.3 [5.2] vs 83.3 [42.2] minutes; P = 0.027). The mean (SD) time to maximal metabolic effect (maximum glucose infusion rate [GIR(max)]) (44.2 [8.6] vs 100.0 [35.6] minutes) and late time to half-maximal effect (101.0 [41.0] vs 257.2 [27.8] minutes) were shorter with oral insulin spray compared with SC insulin (both, P = 0.028). The baseline-corrected GIR(max) (6.8 [3.3] vs 6.2 [2.3] mg/kg . min) and glucose consumption (396.7 [178.0] vs 432.1 [226.0] mg/kg) during the 120 minutes after study drug administration were comparable between oral and SC insulin, respectively. CONCLUSIONS: In this study in a small, selected population of healthy male subjects under euglycemic conditions, oral insulin spray was associated with a higher C(max), shorter T(max), and faster time to peak glucose uptake compared with SC insulin. The short T(max) and the 120-minute duration of effect of oral insulin spray suggest it may be a promising alternative for fulfilling meal-related insulin requirements in persons with diabetes.
Administration, Oral↗
Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria.
Individuals with type 2 diabetes and nephropathy represent a particularly high-risk group for both adverse cardiac as well as renal events. Using the Irbesartan in Diabetic Nephropathy Trial (IDNT) cohort, our objective was to determine baseline characteristics of individuals with type 2 diabetic nephropathy and hypertension predictive for cardiac events. IDNT identified 1715 individuals with type 2 diabetic nephropathy and hypertension having serum creatinine of 1.0 to 3.0 mg/dL and urinary albumin excretion rates > or = 900 mg/day. A cardiovascular (CV) composite was used consisting of CV death, nonfatal MI, hospitalization for heart failure, stroke, amputation, and coronary and peripheral revascularization. Using multivariable Cox regression analysis, 41 baseline characteristics determined a priori were analyzed for their potential relationship to risk of experiencing a CV event. Of the 1715 individuals, 518 (30.2%) had at least one of the CV composite end points. Older age, male gender, longer duration of diabetes, history of cardiovascular disease, history of CHF, high urinary albumin:creatinine ratio, and low serum albumin were strong predictors for CV events; of these, prior history of CVD (RR 2.00, 95% CI 1.63-2.45; P < 0.0001) and high urinary albumin:creatinine ratio (RR 1.29 per natural log unit, 95% CI 1.13-1.48; P = 0.0002) at baseline were highly predictive for cardiovascular events. In conclusion, among individuals with hypertension and diabetic nephropathy, both the degree of albuminuria and lower serum albumin levels provide additional prognostic information concerning cardiovascular risk, in addition to traditional coronary risk factors.
Albuminuria↗
Primary prevention of type 2 diabetes: how do we do it?
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Acarbose↗
[Primary care for type 2 diabetes].
The prevalence of type 2 diabetes is dramatically increasing worldwide and expected to double over the next 25 years, reaching epidemic proportions and thus incurring a considerable financial burden on the health care system. In order to cure the epidemic and minimize expensive complications, a program aimed at optimizing metabolic control and improving surveillance and quality assessment needs to be developed and implemented nation-wide. Most diabetic patients should be treated within the primary care system. In order to meet treatment targets, improve metabolic control and avoid complications, the knowledge and skills needed to treat this chronic disease should be reinforced by dedicated multidisciplinary teams from centers specializing in diabetes care. The specialized diabetes clinics should be devoted to both the treatment of complicated cases of diabetes, that are not achieving treatment targets in the primary care setting, and to the education, updating and empowerment of all primary care teams involved in the treatment of patients with diabetes. A local framework for shared care should be developed through the combined efforts, of the staff of the diabetes center and the primary care physicians and nurses in order to secure the shared goals of optimal treatment and prevention of complications.
Diabetes Mellitus, Type 2↗
Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy.
BACKGROUND: Patients with diabetes have increased risk for adverse cardiovascular events. Angiotensin-converting enzyme inhibitors are protective in type 1 diabetes. However, no definitive studies have examined the use of angiotensin-receptor blockers in patients with type 2 diabetes and overt nephropathy. The primary outcomes of the Irbesartan Diabetic Nephropathy Trial were doubling of serum creatinine levels, end-stage renal disease, and death from any cause. OBJECTIVE: To compare rates of cardiovascular events among patients with type 2 diabetic nephropathy who received conventional antihypertensive therapy with an angiotensin-receptor blocker (irbesartan) or a calcium-channel blocker (amlodipine), or placebo. DESIGN: Randomized double-blind, placebo-controlled trial with a median follow-up of 2.6 years. A time event analysis was used. SETTING: 209 centers in the Americas, Europe, Israel, and Australasia. PARTICIPANTS: 1715 adults with type 2 diabetic nephropathy and hypertension; serum creatinine levels of 89 micromol/L (1.0 mg/dL) to 266 micromol/L (3.0 mg/dL) in women and 106 micromol/L (1.2 mg/dL) to 266 micromol/L (3.0 mg/dL) in men; and urinary protein excretion rates of at least 900 mg/d. INTERVENTION: Treatment with irbesartan, amlodipine, or placebo. MEASUREMENTS: Time to cardiovascular death, myocardial infarction, congestive heart failure, strokes, and coronary revascularization. RESULTS: The three groups were not statistically different in the composite of cardiovascular events. Among the components of the composite, there was a trend toward a decrease in strokes in patients receiving amlodipine versus those receiving placebo (hazard ratio, 0.65 [95% CI, 0.35 to 1.22]; P = 0.18). Likewise, patients receiving amlodipine had a significantly lower rate of myocardial infarction when compared with placebo recipients (hazard ratio, 0.58 [CI, 0.37 to 0.92]; P = 0.02). In contrast, patients receiving irbesartan had a significantly lower incidence of congestive heart failure when compared with placebo recipients (hazard ratio, 0.72 [CI, 0.52 to 1.00]; P = 0.048) or amlodipine recipients (hazard ratio, 0.65 [CI, 0.48 to 0.87]; P = 0.004). CONCLUSION: The composite cardiovascular event rate did not differ in patients with type 2 diabetes and overt nephropathy treated with irbesartan, amlodipine, or placebo in addition to conventional antihypertensive therapy.
Amlodipine↗
Prevalence and risk factors for erectile dysfunction in men with diabetes, hypertension, or both diseases: a community survey among 1,412 Israeli men.
BACKGROUND: Erectile dysfunction (ED) and cardiovascular disease share common risk factors and may be further aggravated by medical treatment for reducing them. HYPOTHESIS: The study was undertaken to assess the prevalence of ED in patients with diabetes (DM), hypertension (HTN), or both diseases, and to evaluate the effect of patient age, medical treatment, and disease duration and control on the prevalence of ED in this population. METHODS: A group of 150 primary practitioners who had patients with known DM and/or HTN conducted a survey, utilizing IIEF-15, a 15-item multidimensional, self-administered questionnaire used for the clinical assessment of ED. RESULTS: In all, 1,412 patients were included: 37% had DM, 38% had HTN, and 25% had both diseases. Their mean age was 55, 58, and 60 years, and 62, 46, and 67% had some degree of ED, respectively. The prevalence of ED increased with age and disease duration in each age group and was higher in subjects with DM than in those with HTN, especially in those aged < 65 years. Poor glycemic control was associated with a higher prevalence rate of ED early in the course of the disease. There was no significant difference in the prevalence of ED according to type and number of antihypertensive drugs. CONCLUSIONS: Erectile dysfunction is common among patients at high risk for cardiovascular disease because of diabetes and/or HTN. Diabetic men are affected earlier than those with HTN. Given the high frequency of ED in young patients with these risk factors, physicians should encourage an open discussion on the subject during routine visits to promote early detection and treatment.
Age Factors↗
Addition of biphasic insulin aspart 30 to rosiglitazone in type 2 diabetes mellitus that is poorly controlled with glibenclamide monotherapy.
BACKGROUND: The incidence of type 2 diabetes mellitus (DM) is rapidly increasing worldwide. Results from large-scale studies show that tight blood glucose (BG) control improves the outcome of patients with type 2 DM. OBJECTIVE: This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione (rosiglitazone [ROS]) to existing sulfonylurea (SU) therapy (glibenclamide) compared with switching to combination treatment with a premixed insulin (biphasic insulin aspart 30 [BIAsp 30], a rapid-acting insulin analog) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy. METHODS: In this 6-week, multicenter, open-label, parallel-group trial, patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy (glycosylated hemoglobin [HbA1c] 8%-13%) were randomized either to replace glibenclamide with BIAsp 30 (individually titrated dosages starting with 6-8 U BID) plus rosiglitazone (4 mg once daily) (BIAsp 30 + ROS group) or to add rosiglitazone (4 mg once daily) to their pretrial doses of glibenclamide (GLIB + ROS group). Patients measured their BG levels immediately before each of the 3 main meals, 90 minutes after the start of each meal, and at bedtime, and mean BG levels were calculated at weeks 0 (baseline), 1, 2, 4, 6, and at 2-week follow-up (week 8). The primary end point was change in mean daily BG level during treatment. Secondary end points included preprandial, postprandial, and bedtime BG levels, serum fructosamine level HbA, and fasting BG level, which were measured at each study visit. Tolerability was assessed using hematologic and biochemical parameters, vital signs, and physical examination. RESULTS: Forty-nine patients (32 men, 17 women; mean [SD] age, 59.1 [8.9] years; mean [SD] body mass index, 27.7 [3.7] kg/m2) participated in the study. A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 (P=0.01). After the 6-week treatment period, change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS (P=0.02). HbA1c decreased in both treatment groups from baseline to study end, but the difference between groups was nonsignificant. The changes in fasting BG from baseline to study end also were nonsignificant between groups. Both combinations were well tolerated. CONCLUSIONS: This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment. The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control.
Adult↗
Insulin-induced hypertension, L-arginine, and endothelial nitric oxide synthase in pregnant rats.
Pregnancy-induced hypertension in rats with chronic exogenous hyperinsulinemia is associated with reduced urinary excretion of nitric oxide metabolites. We tested the hypothesis that there are perturbations of endothelial nitric oxide synthase in their kidneys. We studied three groups of rats: control pregnant rats (n = 6); pregnant rats with hyperinsulinemia by subcutaneous sustained-release insulin pellet (n = 5); and hyperinsulinemic pregnant rats treated with l-arginine 2 gL in drinking water (n = 5). By the end of pregnancy blood pressure was 78 +/- 12 mm Hg in controls, 119 +/- 15 mm Hg in hyperinsulinemic rats, and 77 +/- 8 mm Hg in l-arginine-treated hyperinsulinemic rats, p < 0.007. Serum creatinine was 0.4 mg/dl in controls, 0.6 mg/dl in hyperinsulinemic rats, and 0.5 mg/dl in l-arginine-treated rats, p < 0.05. Corresponding urinary excretion of nitric oxide metabolites was 2.1 +/- 0.5, 1.2 +/- 0.2, and 1.5 +/- 0.2 micromols/mg creatinine, p < 0.01. Expression of endothelial nitric oxide synthase protein in kidneys by Western blot was not different between controls and hyperinsulinemic rats, 5.6 +/- 2.4 and 5.8 +/- 3.4 OD x mm2, but was nearly doubled in l-arginine-treated rats, 10.8 +/- 2.3, p < 0.03. Thus, the salutary effect of l-arginine on hyperinsulinemic pregnancy-induced hypertension (PIH) may be mediated, in part, by endothelial nitric oxide synthase in their kidneys.
Amino Acids, Essential↗
Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys obesus (sand rat).
BACKGROUND: Diabetic nephropathy is caused by multiple factors related to the altered metabolic environment in diabetes mellitus (DM). Experimental diabetic kidney disease is characterized by renal hypertrophy associated with increased tissue concentrations of insulin-like growth factor I (IGF-I). To assess the specific roles of serum insulin and glucose in mediating the development of diabetic nephropathy, the effects of both hyperinsulinaemic and hypoinsulinaemic DM were studied in Psammomys obesus (sand rat), a model of type 2 DM. METHODS: The IGF-I system was studied in normal Psammomys obesus gerbils and at 5, 15 and 70 days after the induction of either hyper- or hypoinsulinaemic DM. To induce hyperinsulinaemic DM, Psammomys were raised on a high-energy diet. Hypoinsulinaemic DM was induced by either administration of streptozotocin or a specially designed diet. RESULTS: Hyperinsulinaemic hyperglycaemic Psammomys did not exhibit renal hypertrophy (unchanged kidney/body-weight ratio) and renal IGF-I levels were in the normal range on days 5, 15 and 70. In contrast, Psammomys with hypoinsulinaemic hyperglycaemia induced either by streptozotocin injection or by pancreas exhaustion brought on by a long-term caloric excess diet, had significant increases in kidney/body-weight ratio which were associated with elevated renal IGF-I and mRNA and protein levels of kidney IGF binding protein I. CONCLUSIONS: This study shows that serum insulin levels in the presence of hyperglycaemia have an important role in the development of experimental diabetic nephropathy in the Psammomys model. The implication of this finding is that the pathophysiological mechanisms for diabetic kidney disease in experimental models may be different for type 1 and type 2 DM.
Animals↗
The emerging role of VEGF in diabetic kidney disease.
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Animals↗
Association of hyperglycemia and insulin with diabetic cardiovascular complications.
Patients with diabetes and/or insulin resistance syndrome are at increased risk for developing cardiovascular disease. The UKPDS raised a great debate about the relative importance of hyperglycemia in the development of cardiovascular disease. Recently, several epidemiologic studies have suggested that high postprandial blood glucose levels are associated with a significant risk for the development of cardiovascular disease well as a grave prognosis for these patients during acute coronary events. In addition, a number of reports reinforce the thesis that postprandial hyperglycemia is a risk factor for mortality. Our review summarizes the current knowledge on the relation between blood glucose, insulin levels, and cardiovascular morbidity and mortality, relating these data to the new World Health Organization and American Diabetes Association classification of disturbed glucose metabolism.
Blood Glucose↗