Duration Of Non-insulin-dependent Diabetes Mellitus Research Articles

Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus.

We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination (baseline) and on three separate occasions during a 48-month follow-up period. All patients had normal urinary albumin excretion (<20 microg/min) at the first three examinations. At the fourth examination (48 months after the first examination), 22 patients had normal urinary albumin excretion and eight had microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min). Compared with patients with normal urinary albumin excretion, patients with microalbuminuria had significantly higher plasma levels of MMP-9 at the second (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14 microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01) examinations, but not at the first examination (34+/-12 microg/L v 33+/-14 microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the occurrence of microalbuminuria within 4 years. The groups did not differ with regard to age, sex, duration of NIDDM, blood pressure, or mean glycated hemoglobin. In addition, the eight patients with microalbuminuria were treated with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily) for 6 months. Microalbuminuria was reduced to within the normal range, and plasma MMP-9 concentrations were significantly decreased with the cilazapril treatment (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1 showed no change during the study period. These data suggest that plasma MMP-9 concentrations preceded and may predict the development of microalbuminuria in NIDDM.

Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.

An increased proportion of fasting proinsulin (PI) relative to immunoreactive insulin (IRI; increased PI/IRI) occurs in noninsulin-dependent diabetes mellitus (NIDDM). To determine whether the magnitude of the increase in PI/IRI is an indicator of the degree of reduced B cell secretory capacity, we measured fasting plasma glucose, PI, IRI, and PI/IRI and related them to maximal B cell secretory capacity (AIRmax) in 9 subjects with NIDDM [age, 61 +/- 3 yr; body mass index (BMI), 27.5 +/- 1.3 kg/m2; duration of NIDDM, 10.8 +/- 1.8 yr; mean +/- SEM] and in 10 healthy subjects matched for age and BMI (age, 61 +/- 6 yr; BMI, 27.9 +/- 1.5 kg/m2). AIRmax was quantified as the incremental insulin response to i.v. arginine at maximal glycemic potentiation (plasma glucose > 25 mmol/L). Mean fasting plasma glucose was 13.7 +/- 1.4 mmol/L (range, 7.5-18.3 mmol/L) in NIDDM subjects and 5.0 +/- 0.1 mmol/L in the controls. Fasting PI was higher in NIDDM (33.1 +/- 5.2) than in controls (9.4 +/- 2.5 pmol/L; P < 0.01), but IRI levels were similar (93.4 +/- 10.9 vs. 82.8 +/- 23.4 pmol/L; P = NS). The PI/IRI ratio was significantly elevated in NIDDM compared to control subjects (35.9 +/- 4.1% vs. 12.8 +/- 0.8%; P < 0.01). After elevation of the glucose level to 30.3 +/- 0.4 mmol/L (NIDDM) and 30.3 +/- 0.5 mmol/L (controls), AIRmax was quantified as 622 +/- 71 pmol/L in NIDDM and 1997 +/- 315 pmol/L in controls, (P < 0.001). The PI/IRI ratio correlated inversely with AIRmax in the NIDDM patients (r = -0.76; P < 0.01). We conclude that the magnitude of the elevation in fasting PI/IRI is related to the reduction in AIRmax. Thus, the fasting PI/IRI ratio appears to be a marker of the degree of reduced AIRmax in NIDDM.

The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature

To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non-insulin-dependent diabetes mellitus (NIDDM) and to quantify the risk. A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies. A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias. Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM.

The Association of Microalbuminuria and Mortality in Non—Insulin-Dependent Diabetes Mellitus

<h3>Objectives:</h3> To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non—insulin— dependent diabetes mellitus (NIDDM) and to quantify the risk. <h3>Methods:</h3> A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies. <h3>Results:</h3> A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias. <h3>Conclusion:</h3> Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM. Arch Intern Med. 1997;157:1413-1418

Vascular complications in relation to ethnicity in non-insulin-dependent diabetes mellitus.

The purpose of this study was to investigate the effect of ethnicity on the development of diabetic retinopathy and nephropathy as markers for microvascular complications and of angina pectoris as a marker for macrovascular complications. We evaluated data from 1124 patients with non-insulin-dependent diabetes mellitus (NIDDM) of Caucasian, Mongoloid, Asian, Armenian, Northern African and Negroid origin who were referred between January 1993 and December 1994. Logistic regression analyses showed that the occurrence of microvascular complications was significantly associated with duration of NIDDM. In addition, retinopathy was significantly associated with glycated haemoglobin A1c (HbA1c) and nephropathy with triglycerides (P < 0.05 and P < < 0.001 respectively). Northern African origin was associated with retinopathy (P < 0.05) and Asian origin with nephropathy (P < 0.005). Macrovascular complication was associated with age and triglyceride level (P < 0.001 and P < 0.05 respectively). Northern African and Negroid ethnicity exclusively did not show a gradual increase in the risk for angina pectoris with increasing age. Moreover, a negative association between Northern African as well as Negroid ethnicity and macrovascular complication was observed (P = 0.05 and P < 0.05 respectively). In support of these observations, we found a favourable lipid profile in both mentioned groups. In summary, we have shown that, in patients with NIDDM, ethnicity is associated with macrovascular complications and duration of the disease with microvascular complications.

Metabolic Control and Prevalent Cardiovascular Disease in Non-Insulin-dependent Diabetes Mellitus (NIDDM): The NIDDM Patient Outcomes Research Team

PURPOSE: Cardiovascular disease is a major cause of morbidity and death in non–insulin-dependent diabetes mellitus (NIDDM). While hyperglycemia is clearly related to diabetic microvascular complications, its contribution to large-vessel atherosclerosis is controversial.PATIENTS AND METHODS: We performed an analysis of the association between glycemic control and prevalent cardiovascular disease in 1,539 participants in the NIDDM Patient Outcomes Research Team study who were under usual care in a health maintenance organization. Prevalent cardiovascular disease and its risk factors were identified by self-administered questionnaire. Cardiovascular disease was defined by the presence of coronary heart disease, peripheral vascular disease, and/or cerebrovascular disease. Glycohemoglobin and lipid levels were obtained from a computerized laboratory database.RESULTS: The mean age of participants was 63 years (range 31 to 91); 51% were women. The mean duration of NIDDM was 9 years (range <1 to 50), 35% took insulin, and 48% took sulfonylureas. Mean glycohemoglobin was 10.6%. Sixty percent had hypertension, 16% currently smoked cigarettes, and the mean total high-density lipoprotein (HDL) cholesterol ratio was 5.7. Fifty-one percent had cardiovascular disease. Cardiovascular disease prevalence remained constant across increasing quartiles of glycohemoglobin for both men and women. In contrast, prevalent cardiovascular disease was associated with established cardiovascular disease risk factors including age (67 versus 59 years, P <0.0001), hypertension (66% versus 54%, P <0.0001), current cigarette smoking (17% versus 13%, P <0.005), and total/HDL cholesterol ratio (5.9 versus 5.6, P <0.05). Cardiovascular disease was also associated with duration of NIDDM (11 versus 8 years, P <0.0001). In multiple logistic regression analysis controlling for established cardiovascular disease risk factors and diabetes duration and therapy, glycohemoglobin remained unassociated with cardiovascular disease.CONCLUSIONS: Glycemic control is not associated with prevalent cardiovascular disease in this large population of individuals with NIDDM. Conventional cardiovascular disease risk factors are independently associated with cardiovascular disease and may be a more promising focus for clinical intervention to reduce atherosclerotic complications in NIDDM.

Severe Periodontitis and Risk for Poor Glycemic Control in Patients with Non-Insulin-Dependent Diabetes Mellitus.

This study tested the hypothesis that severe periodontitis in persons with non-insulin-dependent diabetes mellitus (NIDDM) increases the risk of poor glycemic control. Data from the longitudinal study of residents of the Gila River Indian Community were analyzed for dentate subjects aged 18 to 67, comprising all those: 1) diagnosed at baseline with NIDDM (at least 200 mg/dL plasma glucose after a 2-hour oral glucose tolerance test); 2) with baseline glycosylated hemoglobin (HbA1 ) less than 9%; and 3) who remained dentate during the 2-year follow-up period. Medical and dental examinations were conducted at 2-year intervals. Severe periodontitis was specified two ways for separate analyses: 1) as baseline periodontal attachment loss of 6 mm or more on at least one index tooth; and 2) baseline radiographic bone loss of 50% or more on at least one tooth. Clinical data for loss of periodontal attachment were available for 80 subjects who had at least one follow-up examination, 9 of whom had two follow-up examinations at 2-year intervals after baseline. Radiographic bone loss data were available for 88 subjects who had at least one follow-up examination, 17 of whom had two follow-up examinations. Poor glycemic control was specified as the presence of HbA1 of 9% or more at follow-up. To increase the sample size, observations from baseline to second examination and from second to third examinations were combined. To control for non-independence of observations, generalized estimating equations (GEE) were used for regression modeling. Severe periodontitis at baseline was associated with increased risk of poor glycemic control at follow-up. Other statistically significant covariates in the GEE models were: 1) baseline age; 2) level of glycemic control at baseline; 3) having more severe NIDDM at baseline; 4) duration of NIDDM; and 5) smoking at baseline. These results support considering severe periodontitis as a risk factor for poor glycemic control and suggest that physicians treating patients with NIDDM should be alert to the signs of severe periodontitis in managing NIDDM. J Periodontol 1996;67:1085-1093.

Medial Artery Calcification

Medial artery calcification (MAC) is a nonobstructive condition leading to reduced arterial compliance that is commonly considered as a nonsignificant finding. The aim of our study was to investigate the predictive value of MAC in relation to 7-year cardiovascular mortality, coronary heart disease (CHD) events, stroke, and lower extremity amputation in 1059 patients (581 men and 478 women) with non-insulin-dependent diabetes mellitus (NIDDM). At baseline radiologically detectable MAC in femoral arteries was found in 439 patients (41.5%) and intimal-type calcification in 310 diabetic patients (29.3%). The mean fasting plasma glucose at baseline was somewhat higher in women and the duration of diabetes somewhat longer in patients with MAC than in those without, but otherwise the presence of MAC was unrelated to conventional cardiovascular risk factors. During the follow-up 305 diabetic patients died: 208 from cardiovascular disease, 158 from CHD, and 34 from stroke. Furthermore, 58 NIDDM patients underwent their first lower extremity amputation. MAC was a strong independent predictor of total (risk factor-adjusted odds ratio and 95% confidence interval: 1.6; 1.2, 2.2), cardiovascular (1.6; 1.1, 2.2), and CHD (1.5; 1.0, 2.2) mortality, and it was also a significant predictor of future CHD events (fatal or nonfatal myocardial infarction), stroke, and amputation. This relationship was observed regardless of glycemic control and known duration of NIDDM. MAC is a strong marker of future cardiovascular events in NIDDM unrelated to cardiovascular risk factors, supporting the hypothesis that reduced arterial elasticity could lead to clinical manifestations of diabetic macroangiopathy.

The influence of hyperglycaemia upon the colour vision of patients with diabetes mellitus

Purpose: To investigate whether an increase in plasma glucose level had an influence upon the colour vision of patients with non-insulin dependent diabetes mellitus (NIDDM). Methods: A total of 16 patients with NIDDM were investigated, mean age and duration of NIDDM 59.8 and 4.7 years, respectively. The colour vision was assessed every 30 minutes for 4 hours using a Desaturated D15 under three conditions: (1) meal tolerance test (n = 8); (2) stable plasma glucose conditions, i.e. fasting (n = 8); and (3) intravenous glucose tolerance test (n = 8). Results: The total error score does not vary significantly under the three test conditions. The influence of the plasma glucose upon the TES is not significant, even though levels of up to 22.7 mmol/l were recorded. Conclusion: Colour vision does not appear to be influenced by acute increases in plasma glucose concentrations, unlike the deterioration of colour vision found during hypoglycaemia.

The influence of hyperglycaemia upon the colour vision of patients with diabetes mellitus

Purpose: To investigate whether an increase in plasma glucose level had an influence upon the colour vision of patients with non‐insulin dependent diabetes mellitus (NIDDM).Methods: A total of 16 patients with NIDDM were investigated, mean age and duration of NIDDM 59.8 and 4.7 years, respectively. The colour vision was assessed every 30 minutes for 4 hours using a Desaturated D15 under three conditions: (1) meal tolerance test (n = 8); (2) stable plasma glucose conditions, i.e. fasting (n = 8); and (3) intravenous glucose tolerance test (n = 8).Results: The total error score does not vary significantly under the three test conditions. The influence of the plasma glucose upon the TES is not significant, even though levels of up to 22.7 mmol/l were recorded.Conclusion: Colour vision does not appear to be influenced by acute increases in plasma glucose concentrations, unlike the deterioration of colour vision found during hypoglycaemia.

Hypertension, hyperlipidemia, and abdominal obesity and the development of microalbuminuria in patients with non-insulin-dependent diabetes mellitus.

The hyperlipidemia syndrome (also called syndrome X or the deadly quartet) is a recognized constellation known to increase cardiovascular mortality, but its effect on renal decline is not well-described. This study examined the differential effects of hypertension, hyperlipidemia, and abdominal obesity on overnight urinary albumin excretion ratios (UAERs) among patients with non-insulin-dependent diabetes mellitus (NIDDM), who by definition possess the remaining component of the syndrome, insulin resistance. We conducted a survey of 317 primary care NIDDM patients measuring waist-to-hip ratios, fasting lipid levels and glycemic values, and overnight UAERs. The study was carried out between January 1989 and June 1991. Using logistic regression controlling for age, race, sex, duration of NIDDM, and smoking status, elevated glycosylated hemoglobin (odds ratio [OR] = 1.95, 95 percent confidence interval [CI] = 1.16-3.27) or the addition of one component of the deadly quartet to pure diabetes doubled or tripled the odds of an elevated UAER (NIDDM plus obesity OR = 2.00, 95 percent CI = 1.02-3.93; NIDDM plus hypertension OR = 3.45, 95 percent CI = 1.38-8.63; NIDDM plus hyperlipidemia OR = 1.60, 95 percent CI = 0.53-4.81). In a dose-response manner, two additional factors exerted additive effects; all three additional factors combined with pure NIDDM multiplied the effect, with an odds ratio of 9.34 (95 percent CI = 2.24-38.9). These data quantify the incremental effects of abdominal obesity, hypertension, and hyperlipidemia on abnormal UAERs among NIDDM patients and strongly suggest the need for aggressive and simultaneous correction of multiple risk factors to prevent end organ damage in this population.

Measurement of soluble thrombomodulin in sera from various clinical stages of diabetic nephropathy.

The levels of soluble thrombomodulin (TM) in serum samples were measured by one-step sandwich enzyme immunoassay. The aim of the present study was to determine if levels of soluble TM in sera might correlate with disease activity in patients with diabetic nephropathy. Three hundred and twenty patients with diabetic nephropathy were examined. Patients with diabetic retinopathy were excluded from the present study. This study showed an increase of soluble TM levels in sera from patients with diabetic nephropathy. The levels of soluble TM in sera from the macroalbuminuric stage with renal dysfunction were significantly increased compared with those from the normo-, micro-, or macroalbuminuric stage of diabetic nephropathy without renal dysfunction. The increase of soluble TM in sera paralleled levels of urinary albumin, blood urea nitrogen (BUN), s-creatinine (Cr), and duration of noninsulin-dependent diabetes mellitus (NIDDM). Furthermore, a decrease of TM staining in the glomerular capillary walls was observed in both microalbuminuric and macroalbuminuric stages by immunofluorescence. It appears that the measurement of soluble TM in sera is useful in evaluating the degree of glomerular endothelial injuries in patients with diabetic nephropathy.

Age as a determinant of glomerular filtration rate in non-insulin-dependent diabetes mellitus

The level of glomerular filtration rate (GFR) and its determinants in non-insulin-dependent diabetes mellitus (NIDDM) are currently controversial. We measured GFR and effective renal plasma flow (ERPF) in 121 consecutive NIDDM without evidence of overt diabetic nephropathy. Age varied from 28 to 70 years, 61.2% were women and known duration of NIDDM was 0-37 years. Hypertension was detected in 36.4% of patients and 47.8% had microalbuminuria. An inverse correlation was found between GFR and age, but not with known duration of NIDDM: It was a weak correlation (r = -0.41) but statistically significant (P < 0.001). The other variables considered were not significant by multiple stepwise regression analysis, but patients with lower GFR tended to have diabetic retinopathy more frequently. GFR was lower in hypertensive compared to normotensive patients (123 +/- 28.4 versus 136 +/- 32.5 ml/min/1.73 m2; P < 0.05), but was not different between patients with normal and elevated albumin excretion rate. ERPF also had an inverse correlation with age (r = -0.45, P < 0.001). We conclude that (i) age should be considered as a confounding variable when evaluating GFR in patients with NIDDM, and (ii) the age-dependent decline in GFR may mask hyperfiltration in the early stages of diabetic nephropathy in NIDDM:

Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota.

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P less than .01); older age at onset of diabetes (P less than .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

Community-based exercise intervention: Zuni Diabetes Project.

Non-insulin-dependent diabetes mellitus (NIDDM) is a serious health problem among the Zuni Indians of New Mexico. In July 1983, Indian Health Service personnel initiated a community-based exercise program designed to help control NIDDM in the community. To retrospectively evaluate the effects of the exercise program, the medical records of 30 participants with NIDDM were compared with the medical records of 56 nonparticipants with NIDDM matched by age, sex, health-care provider, and duration of NIDDM. From 1 July 1983 through 1 October 1985, participants had a mean weight loss of 4 kg, whereas nonparticipants had a mean weight loss of 0.9 kg (P less than .05). Participants' fasting blood glucose values dropped by a mean of 43 mg/dl, compared to a mean drop of 2 mg/dl among the nonparticipants (P less than .05). Participants were significantly more likely than nonparticipants to have stopped their hypoglycemic medication (relative risk 4.2) and to have decreased their medication dosage (relative risk 2.2). These results suggest that participation in a community-based exercise program can produce significant weight loss and improvement in glycemic control among a group of Native Americans with NIDDM.