Main Risk Factors for Nephropathy in Type 2 Diabetes Mellitus


Synopsis: The greatest risk factors for a decline in renal function and an increase in microalbuminuria in patients with type 2 diabetes are plasma cholesterol levels, mean blood pressure, and hyperglycemia.

Source: Ravid M, et al. Arch Intern Med 1998;158:998-1004.

The importance of tight glycemic control in reducing microvascular complications in insulin-dependent diabetes mellitus is well-established, based on the results of the Diabetes Control & Complications trial.1 Similar studies in type 2 diabetes mellitus, however, have been inconclusive. Thus, Ravid and associates undertook this prospective, long-term study 1) to assess the influence of glycemic control, mean blood pressure, plasma lipids, and other risk factors on the development and progression of diabetic nephropathy; and 2) to evaluate the correlations between these parameters and arteriosclerotic cardiovascular disease.

The study included 574 patients, aged 40-60 years, with recent onset of type 2 diabetes mellitus (< 5 years) who fulfilled the three major inclusion criteria: 1) normal renal function (serum creatinine < 1.4 mg/dL); 2) normotension (BP < 140/90 or mean arterial pressure < 107 mmHg); and 3) normal urinary albumin excretion (UAE < 30 mg/24 hr). Hemoglobin AIC (HbAIC) and plasma lipids (including total cholesterol, HDL, LDL, and triglycerides) were measured periodically in addition to blood pressure and body mass index (BMI). Renal function was evaluated using the UAE and the decline in reciprocal creatinine values. Cigarette smoking and socioeconomic status were also recorded. Final outcomes included definite clinical events including death, nonfatal myocardial infarction, angina pectoris, congestive heart failure, and peripheral vascular disease.


Association of baseline parameters with the risk to develop microalbuminuria and to reach cardiovascular end points

Risk (Odds Ratio)*
To Develop                            To Reach 
Microalbuminuria                Cardiovascular 
                                             End Points
1. Male gender
4.3                                          2.3
2. Smoker
6.0                                          2.1
3. BMI >= 25 kg/m2
9.9                                          7.6
4. HbAIC >= 0.09
8.5                                          7.0
5. Mean BP >= 95 mmHg
9.8                                        20.2
6. Total cholesterol >= 203 mg/dL
20.6                                        11.5
7. HDL < 44 mg/dL
7.8                                           5.0
8. LDL ³ 124 mg/dL
6.2                                         14.3
9. High risk patients_
42.7                                       14.8

    * Confidence intervals (not shown) were statistically significant at P < 0.001 for microalbuminuria and P < 0.005 for cardiovascular end points

    _ High risk patients: combination of 4, 5, & 6

The mean duration of follow-up was 7.8 years (range, 2-9 years). At the end of the study, 65% still had normal UAE, while 19% had microalbuminuria (30-300 mg/24 hr) and 16% had overt albuminuria (> 300 mg/24 hr). The correlation between HbAIC and the risk of albuminuria was exponential. There were three baseline parameters together, identifiable by multiple logistic regression, that marked the high-risk group that was at the greatest risk of decline in renal function and increase in albuminuria in type 2 diabetes mellitus: 1) total cholesterol of 203 mg/dL or greater; 2) mean blood pressure of 95 mmHg or greater; and 3) HbAIC of 0.09 or greater. These 151 high-risk patients comprised 27% of the total patient group and had an odds ratio of 43 for diabetic nephropathy and 15 for clinical events for arteriosclerotic cardiovascular disease, compared to the rest of the group. Other correlations were as expected and are shown in the table.


How very useful it is to back up medical common sense with true science. The data from numerous studies have suggested the importance of glycemic control, blood pressure control, and lipid values in diabetic management. Our typical high risk patient with the highest risk for both microvascular and microvascular complications in diabetes mellitus is thus easily identified: HbAIC of 0.09 or greater; mean blood pressure of 95 mmHg or greater (> 130/80 mmHg); and total cholesterol of 203 mg/dL or greater (LDL ³ 124 mg/dL). The treatment strategies emerge clearly: tighter glycemic control, normalization of blood pressure, and lowering of lipid levels. Of course, patients must be encouraged to exercise and lose weight if obese, eat healthfully, and stop smoking.

Diabetic nephropathy remains the leading cause of end stage renal disease in the United States, with an annual cost of 13.1 billion dollars in 1995.2 This, of course, is only the cost of medical care and does not include emotional costs, psychological scars, and work force losses. Much can be done, but early interventions such as glucose, blood pressure, and lipid control are needed to preserve the quality of life of our type 2 diabetic patients.


    1. N Engl J Med 1993;329:977-986.

    2. USRDS 1997 Annual Data Report.