Measures of Kidney Function and Damage Not Associated with Rate of Incident Type 2 Diabetes

Common risk factors for chronic kidney disease (CDK) and type 2 diabetes mellitus (T2DM) often overlap, suggesting that the risk for diabetes may be increased in patients with CKD. There have been only few studies among patients with CKD prior to progression to end-stage renal disease (ESRD) to examine whether the risk for diabetes is increased in the patient population.

In the general population, there are a number of models predicting the risk for T2DM; the models commonly include a number of well-established risk factors that are identified either in the course of a standard clinical visit or through standard blood tests. There are no models for diabetes risk that incorporate kidney function and damage for use in patients with CKD prior to ESRD. Further, it is unclear which measure of glycemic control (fasting blood glucose level, hemoglobin A1c level [HbA1c], or insulin resistance) is the optimum measure to use to define and predict diabetes in the setting of CKD.

Christopher Jepson, PhD, and colleagues recently conducted a prospective cohort study to examine rates of incident T2DM among patients with CKD who were enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. CRIC is a long-term observational cohort study. The researchers for the current study aimed to (1) estimate the unadjusted incidence of T2DM; (2) examine the concordance among several measures of glycemic control; (3) identify factors associated with incident T2DM; and (4) examine the predictive performance of multivariable models of incident T2DM, including measures of kidney function and damage in addition to established T2DM risk factors, and using various measures of glycemic control. Results of the study were reported in the American Journal of Kidney Diseases [2019;73(1):72-81].

The outcome of interest was incident T2DM, defined as fasting blood glucose ≥126 mg/dL or prescription of insulin or oral hypoglycemic agents.

The first cohort of the CRIC study was recruited from July 2003 to September 2008 and included 3939 participants. Of those, 2064 were categorized as having diabetes at baseline. Of the remaining 1875, 91.4% (n=1713) had complete data for all variables that were included in the final multivariable models. That group and 162 with partial data were compared on baseline characteristics and unadjusted risk for incident T2DM. There were no significant differences between the two groups in sex, family history of diabetes mellitus, use of blood pressure or lipid-lowering medications, body mass index, triglyceride level, age, estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), homeostatic model assessment of insulin resistance (HOMA-IR), or HbA1c; there was also no difference in unadjusted risk for incident T2DM.

The 1713 participants with full data were used as the analysis sample in the current study. Of those 1713 individuals, 81.8% (n=1402) were categorized as normoglycemic and 18.2% (n=311) were characterized as prediabetic at baseline.

In the sample of 1713 individuals, 11.85% (n=203) developed incident T2DM during a mean 6.65 years of follow-up, over a total of 11,399 person-years. The overall unadjusted incidence rate of incident T2DM was 17.81 cases per 1000 person-years. When participants who developed T2DM following onset of ESRD were included, the rate was 18.95 per 1000 person-years. The rate among participants with baseline fasting blood glucose levels <100 mg/dL was 12.17; among those with levels between 100 and 125 mg/dL, the rate was 46.55.

Using the American Diabetes Association definitions of prediabetes (HbA1c of 5.7%-6.4%, fasting blood glucose of 100-125 mg/dL), a higher percentage of the analysis sample was classified as having prediabetes at baseline by a single measurement of HbA1c than by a single fasting blood glucose measurement (47.3% and 18.2%, respectively). The simple k coefficient for these two measurements was 0.13. (HOMA-IR was not included in the analysis of concordance because there are no standard criteria for prediabetes and diabetes for this measure.)

Of the 1402 participants classified as normoglycemic at baseline by fasting blood glucose level, those who were classified as having prediabetes by HbA1c level (n=609) scored significantly lower than those classified as normoglycemic than those classified as normoglycemic by HbA1c level on measures of baseline glycemic control (fasting blood glucose and HOMA-IR) and significantly higher on numerous baseline measures of risk factors for T2DM. They also had significantly greater unadjusted risk for incident T2DM.

There was a significant association between higher values of each of the indicators of glycemic control (fasting blood glycose, HOMA-IR, and HbA1c) and higher unadjusted rates of incident T2DM. There was no significant association between the two indicators of kidney function and damage (eGFR and UAC) and incident T2DM.

In analysis restricted to the normoglycemic participants, the most significant contribution to the multivariable cause-specific hazards model was fasting blood glucose. The hazard ratio (HR) associated with a 1-standard deviation increase in fasting blood glucose level was 1.407 (95% confidence interval [CI], 1.135-1.744; P=.002). Family history of diabetes was the only other predictor that contributed significantly (HR, 1.50; 95% CI, 1.033-2.172; P=.03).

The researchers cited some limitations to the study, including the relatively low number of events observed, which diminished the power of all analyses; limiting predictors to measures performed at baseline; and the possibility that there may have been important risk factors not measured in the study.

In conclusion, the researchers said, “The rate of incident T2DM among individuals with CKD is markedly higher than in the general population, supporting greater vigilance in this subpopulation. Concordance between measures of baseline glycemic control was low. In multivariable models of T2DM risk among individuals who were normoglycemic at baseline, measures of kidney function and damage were not associated with incident T2DM and did not  improve the capacity of the models to predict T2DM. Baseline glycemic control and family history of diabetes mellitus were the only factors detected to be predictive of incident T2DM. These models displayed moderate predictive performance.”

Takeaway Points

1. Researchers conducted a study designed to examine rates of and risk factors for incident type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort study.
2. The overall T2DM incidence rate was 17.81 cases per 1000 person years. Concordance between fasting blood glucose and hemoglobin A1c levels was low.
3. There was no significant association between measures of kidney function and damage and incident T2DM.