Achieving Glycemic Control HbA1c less than 7 percent Linked to Reduction risk of Diabetes-Related Complications

Several microvascular and macrovascular complications are linked to poorly managed type 2 diabetes (T2D). The prevalence of chronic diabetic sequelae among Indians with T2D varied from 4.8 to 21.7% for retinopathy, 0.9 to 62.3% for nephropathy, and 10.5 to 44.9% for neuropathy. In T2D, macrovascular complications have been reported to be the most frequent cause of morbidity and mortality, with all complications independently predicting mortality. (1)

When taking into account the provided scenario, Boye K.S. et al retrospective's analysis revealed that keeping all hemoglobin A1c (HbA1c) levels below 7% decreased the likelihood of being diagnosed with cardiovascular disease by 24%, metabolic disease by 63%, neuropathy by 38%, nephropathy by 19%, and peripheral vascular disease by 48%, respectively, in T2D patients. (2)

Glycemic Control & Diabetes Complications- Associative Evidence (2)

Several clinical studies have indicated that stringent glycemic control may attenuate the problems related to T2D. Along this line, Boye K.S. et al. conducted a retrospective analysis to extend the evidence from clinical trials and provide updated evidence of the association between glycemic control and diabetes-related complications in people with T2D in the US between 2007 and 2020.

Adults with T2D were analyzed using the Optum Clinformatics Data Mart (CDM) database, which was available from 2007 to 2020. Individuals were categorized as having poor glycemic control (HbA1c greater than or equal to 7%) or sustained glycemic control (HbA1c less than 7%) across the 5-year post-period. The relationship between sustained glycemic control and identification of diabetes-related complications post-period was investigated using multivariable analysis. The salient findings of the study showed:

• Three thousand and sixty-seven individuals were included in the final sample, the mean age was 66.5 years, 60% were female.
• Over half of those in the final sample had visited a cardiologist in the pre-period, and, on average, individuals were treated in the pre-period with 1.8 classes of glucose-lowering agents (GLAs) and 13.1 non-GLA drugs.
• Individuals with sustained glycemic control, defined as all HbA1c less than 7% in the post-period, compared to those with sustained sub-optimal glycemic control, defined as all HbA1c greater than equal to 7% in the post-period, were significantly less likely to be diagnosed in the post-period with most of the diabetes-related comorbidities of interest.
• In particular, maintaining HbA1c less than 7% in the 5-year post-period was associated with a significantly lower likelihood of being diagnosed with: cardiovascular disease (24% lower odds, odds ratio [OR] = 0.76, 95% confidence interval [CI] 0.61–0.94), metabolic disease (63% lower odds, OR = 0.37, 95% CI 0.22–0.60), neuropathy (38% lower odds, OR = 0.62, 95% CI 0.45–0.84), nephropathy (19% lower odds, OR = 0.81, 95% CI 0.69–0.94), and peripheral vascular disease (48% lower odds, OR = 0.52, 95% CI 0.33–0.83).

The result is generally in line with the overall findings of the clinical trials conducted as part of the Veterans Affairs Diabetes Trial (VADT), Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, and the United Kingdom Prospective Diabetes Study (UKPDS), all of which reported statistically significant decreases in microvascular complications with intensive glycemic control.

According to the UKPDS, intensive pharmacological therapy (median HbA1c 7%) resulted in a 25% lower overall rate of microvascular complications than conventional treatment (medianHbA1c] 7.9%) after a median follow-up period of 10 years. Later T2D clinical studies included individuals with long-standing diabetes and a history of, or risk factors for, vascular disease, in contrast to the UKPDS, which only included individuals with newly diagnosed T2D. ADVANCE research (2008), one of these later trials, indicated that an intensively treated cohort (mean HbA1c of 6.5%) compared to a conventional therapy cohort (mean HbA1c of 7.3%) saw a statistically significant decrease in the rate of microvascular events, but not macrovascular events.

Sustained Glycemic Control & Its Relation to Macrovascular Complications: (2)

In particular, the present study's macrovascular findings—that is, the sustained HbA1c less than 7% lowers the odds of being diagnosed with two macrovascular complications, specifically peripheral vascular disease and cardiovascular disease—over a 5-year time horizon—generally support a number of earlier non-clinical studies. Those who were initially assigned to the intensive treatment cohort showed statistically significant lower rates of myocardial infarction and all-cause death, according to ten years of additional observational follow-up after UKPDS, and ten years of additional observational follow-up after VADT showed a significant decrease in the risk of cardiovascular events in the intervention group compared to the control group.

These studies showed that compared to having sustained HbA1c at above 7%, keeping an HbA1c of less than 7% over five years was associated with a lower incidence of vascular complications connected to diabetes. This is consistent with the most recent American Diabetes Association guidance, which states that the glycemic (HbA1c) target for individuals (nonpregnant) with diabetes is less than 7.0%. (3)

Role of Therapeutic Lifestyle Modifications (TLM): A return of HbA1c level at less than 6.5%, remission of diabetes, is achievable in people with T2D. Studies have emphasized the central role of weight loss and lowering carbohydrate intake for the remission of diabetes. (3) For newly diagnosed diabetes, sustained remission is achievable if carbohydrate content is reduced to 49-54%, while a 50-60% reduction is suggested for the remission of pre-diabetes to normal glucose tolerance. Similarly, within six years of diagnosis, a structured primary care-based weight management programme can sustain remission to a non-diabetic condition, with persistent remission correlated with sustained weight loss. (4)

In conclusion, the benefits of stringent glycemic control led to a decrease in the rates of microvascular complications as well as noteworthy favorable benefits in cardiovascular events and overall mortality. In India, during the past few years, pre-diabetes and diabetes incidence rates have increased. To reduce the burden of chronic consequences in people with type 2 diabetes, achieving target blood sugar glucose HbA1c levels of less than 7% might be seen as a crucial strategy.

References:

1. S. Govindaswamy, Dhivya P.S . Prevalence and complications of diabetes mellitus In India - A systematic review. Research Square, 2022. doi.org/10.21203/rs.3.rs-1292516/v

2. Boye KS, Thieu VT, Lage MJ, Miller H, Paczkowski R. The Association Between Sustained HbA1c Control and Long-Term Complications Among Individuals with Type 2 Diabetes: A Retrospective Study. Adv Ther. 2022;39(5):2208-2221. doi:10.1007/s12325-022-02106-4

3. Diabetes Care 2021;44(Supplement_1):S73–S84. doi.org/10.2337/dc21-S006

4. Ranjit Mohan Anjana, Seshadhri Srinivasan, Vasudevan Sudha, et.al, ICMR-INDIAB Collaborative Study Group; Macronutrient Recommendations for Remission and Prevention of Diabetes in Asian Indians Based on a Data-Driven Optimization Model: The ICMR-INDIAB National Study. Diabetes Care 2022; dc220627. https://doi.org/10.2337/dc22-0627