worldwide. It has affected about 285 million patients in 2010 and is
expected to reach 439 million by 2030. The globalization of the diabetes
epidemic, given its micro- and macrovascular problems, imposes enormous
economic burden on patients and healthcare systems in both developed
and developing economics. Among the diabetic microvascular diseases,
chronic kidney disease (CKD) presents unique challenges. Diabetes is the
leading cause of end stage renal disease (ESRD). Chronic kidney disease
contributes to the development of cardiovascular disease and therefore
increases the risk of death and cardiovascular events. Approximately 40 %
of patients with type 2 diabetes have higher urinary albumin excretion
consistent with underlying renal disease and 17% of patients with
diabetes have CKD. Intensive glycemic control may play a vital role to
halt or slow down the advancement of diabetic kidney disease.
Anti-hyperglycemic agents in these patients are inadequate due to safety
and tolerability concerns. Metformin, sulfonylureas and thiazolidione
are connected with an increased incidence of hypoglycemia, weight gain
and lactic acidosis in patients with type 2 diabetes and CKD. Patients
with type 2 diabetes and CKD do not achieve or maintain adequate
glycemic control. The use of metformin in CKD patients is controversial,
and is even on FDA black box warnings as causing lactic acidosis, which
is rare but potentially fatal. A previous study (ADVANCE) proved that
intensive glucose control in type 2 diabetes patients drastically
decreased the risk of renal outcomes, including new or worsening
nephropathy and ESKD.
The purpose of this study was to find out if long-term intensive glycemic control can lead to ESKD. ADVANCE-surviving patients were recruited for ADVANCE–ON, a post-trial study. HbA1c fasting blood glucose, blood pressure, weight, and serum creatinine of patients were assessed at their first post-trial and then annually. The cause of death for patients who died was recorded. Telephone or home visits are offered to patients who cannot do a follow-up. The study outcome was ESKD, stroke, cardiovascular death, myocardial infarction and hypoglycemia. Cumulative incidence survival curves and Cox proportional hazards models were some of the statistical methods used. The patients end points of the date of death, date of last visit, and date of vital status were noted.
Of the 8,494 patients, 4,283 of them did intensive glycemic treatment while 4,211 underwent the standard glucose control. Of these, 5,131 of them completed their visit. The post-trial follow-up of 5.4 years, gliclazide modified release, metformin, insulin, glitazones and glucosidase inhibitors are used in both intensive and standard glucose with an HbA1c of (0.67%, 95% CI 0.64, 0.70 P<0.001) was observed at the end of randomized therapy. 2.9 years later, the post-trial visit had (0.08% 95% CI -0.07, 0.22 P =0.29). There was a rise in HbA1c in the intensive control group versus the standard group. The HbA1c levels of the two groups converged at the post-trial visit (7.3% vs 7.3%, P=0.29). 27 patients recorded ESKD during in-trial events and 37 of the patients died due to renal causes. 55 patients recorded ESKD during post-trial and 64 died due to renal causes. There was a drastic decrease in the risk of ESKD witnessed in intensive glucose control in trial period. (7 vs 20 events, HR 0.35 95%CI 0.15, 0.83 P=0.02). These values persisted after 9.9 years of follow-up (29 vs 53, HR 0.54 95% CI 0.34, 0.85 P< 0.01). Over the 9.9 years, 194 patients needed to be treated with intensive glucose control to prevent one ESKD event. Also, the number needed to be treated by CKD stage was 109 for CKD stages 1 and 2 and 393 for CKD stage 3 or more.
In conclusion, it was clear that intensive glucose control had no effect on overall cardiovascular death, all-cause mortality, myocardial infarction, or stroke. Also, baseline CKD status had no effect on intensive glucose control on these outcomes. However, control continues to protect against the development of ESKD in type 2 diabetes patients, but the patients with most benefit are those with preserved kidney function. The weakness of this study includes the non-adjudicated renal end points and lack of complete biochemical data for all patients during the post-trial follow-up.
Practice Pearls:
The purpose of this study was to find out if long-term intensive glycemic control can lead to ESKD. ADVANCE-surviving patients were recruited for ADVANCE–ON, a post-trial study. HbA1c fasting blood glucose, blood pressure, weight, and serum creatinine of patients were assessed at their first post-trial and then annually. The cause of death for patients who died was recorded. Telephone or home visits are offered to patients who cannot do a follow-up. The study outcome was ESKD, stroke, cardiovascular death, myocardial infarction and hypoglycemia. Cumulative incidence survival curves and Cox proportional hazards models were some of the statistical methods used. The patients end points of the date of death, date of last visit, and date of vital status were noted.
Of the 8,494 patients, 4,283 of them did intensive glycemic treatment while 4,211 underwent the standard glucose control. Of these, 5,131 of them completed their visit. The post-trial follow-up of 5.4 years, gliclazide modified release, metformin, insulin, glitazones and glucosidase inhibitors are used in both intensive and standard glucose with an HbA1c of (0.67%, 95% CI 0.64, 0.70 P<0.001) was observed at the end of randomized therapy. 2.9 years later, the post-trial visit had (0.08% 95% CI -0.07, 0.22 P =0.29). There was a rise in HbA1c in the intensive control group versus the standard group. The HbA1c levels of the two groups converged at the post-trial visit (7.3% vs 7.3%, P=0.29). 27 patients recorded ESKD during in-trial events and 37 of the patients died due to renal causes. 55 patients recorded ESKD during post-trial and 64 died due to renal causes. There was a drastic decrease in the risk of ESKD witnessed in intensive glucose control in trial period. (7 vs 20 events, HR 0.35 95%CI 0.15, 0.83 P=0.02). These values persisted after 9.9 years of follow-up (29 vs 53, HR 0.54 95% CI 0.34, 0.85 P< 0.01). Over the 9.9 years, 194 patients needed to be treated with intensive glucose control to prevent one ESKD event. Also, the number needed to be treated by CKD stage was 109 for CKD stages 1 and 2 and 393 for CKD stage 3 or more.
In conclusion, it was clear that intensive glucose control had no effect on overall cardiovascular death, all-cause mortality, myocardial infarction, or stroke. Also, baseline CKD status had no effect on intensive glucose control on these outcomes. However, control continues to protect against the development of ESKD in type 2 diabetes patients, but the patients with most benefit are those with preserved kidney function. The weakness of this study includes the non-adjudicated renal end points and lack of complete biochemical data for all patients during the post-trial follow-up.
Practice Pearls:
- CKD is the leading cause of end stage renal disease worldwide and contributes to the development of cardiovascular diseases, thus increasing the risk of death and cardiovascular events.
- Intensive glycemic control in type 2 diabetes decreased drastically the primary composite outcome of microvascular events mainly as consequence of a reduction in nephropathy.
- Type 2 diabetes patients who benefit the most are those with preserved kidney function. Intermediate effects in in the group were those with CKD stage 1 and 2 and a lesser effects in CKD stage 3 or greater at baseline.
No comments:
Post a Comment