See also (4) Links To The Complete “Standards Of Medical Care In Diabetes – 2018” With Link To The Update And Additional Resources Posted on October 16, 2018 by Tom Wade MD.
In my next few posts I’m reviewing Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [PubMed Abstract] [Full Text HTML] [Full Text PDF].
In this post I’m reviewing some resources on the effects of tight glucose control on the prevention of microvascular complications and macrovascular complications.
Here are some excerpts from Resource (1):
The rationale, importance and context
of glucose-lowering treatment
Marked hyperglycaemia is associated with symptoms including
frequent urination, thirst, blurred vision, fatigue and
recurring infections. Beyond alleviating symptoms, the aim of
blood glucose lowering (hereafter, referred to as glycaemic
management) is to reduce long-term complications of diabetes.
Good glycaemic management yields substantial and enduring
reductions in onset and progression of microvascular
complications. This benefit has been demonstrated most clearly
early in the natural history of the disease in studies using
metformin, sulfonylureas and insulin but is supported by more
recent studies with other medication classes. The greatest absolute risk reduction (ARR) comes from improving poor
glycaemic control, and a more modest reduction results from
near normalisation of glycaemia . The impact of glucose
control on macrovascular complications is less certain.*
*[Emphasis added]. That bolded statement is a very deliberate understatement on the part of the authors. The older data strongly suggests that tight glucose control does not impact the rate of macrovascular complications. However, there is hope for the future. See Implications of new evidence from cardiovascular outcomes trials from Resource (1) which I’ve included right after the excerpts from Resource (2).
Here are some excerpts from Resource (2) below, Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Ann N Y Acad Sci. 2013 Apr;1281:36-50. doi: 10.1111/nyas.12044. Epub 2013 Feb 6:
The relationship between glucose control and cardiovascular outcomes in type 2 diabetes has been a matter of controversy over the years. Although epidemiological evidence exists in favor of an adverse role of poor glucose control on cardiovascular events, intervention trials have been less conclusive. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, the Action in Diabetes and Vascular Disease (ADVANCE) study, and the Veterans Affairs Diabetes Trial (VADT) have shown no beneficial effect of intensive glucose control on primary cardiovascular endpoints in type 2 diabetes. However, subgroup analysis has provided evidence suggesting that the potential beneficial effect largely depends on patients’ characteristics, including age, diabetes duration, previous glucose control, presence of cardiovascular disease, and risk of hypoglycemia.
Cardiovascular disease (CVD) is the major cause of death in patients with type 2 diabetes (T2D), as more than 60% of T2D patients die of myocardial infarction (MI) or stroke, and an even greater proportion of patients have serious burdensome complications.1 The impact of glucose lowering on cardiovascular complications is a hotly debated issue. The United Kingdom Prospective Diabetes Study (UKPDS) was the first clinical trial to provide key evidence of the importance of using intensive therapy for diabetes control in individuals with newly diagnosed T2D. However, although the insulin or sulphonylurea-based intensified glucose-control treatment was effective in reducing the risk of major microvascular endpoints, the effects on CVD risk were modest and did not reach statistical significance.2 Recent large clinical trials (often referred to as “megatrials”), the Action in Diabetes and Vascular Disease (ADVANCE),3 Action to Control Cardiovascular Risk in Diabetes (ACCORD),4 and the Veterans Affairs Diabetes Trial (VADT),5reported no significant decrease in primary cardiovascular endpoints with intensive glucose control.
Several recent meta-analyses of randomized controlled trials have also investigated the effects of intensive glucose lowering on all-cause mortality, cardiovascular death, and vascular events in T2D.6–10 In the largest and most recent meta-analysis by Boussageon et al., 13 studies were included.6 Of the 34,533 patients evaluated, 18,315 received intensive glucose-lowering treatment and 16,218 standard treatment. Intensive treatment did not significantly affect all-cause mortality or cardiovascular death. The results of this meta-analysis showed limited benefit of intensive glucose-lowering therapy on all-cause mortality and deaths from cardiovascular causes, and a 10% reduction in the risk of microalbuminuria.6 Results from other meta-analyses have also shown no effects of intensive glucose control on all-cause or cardiovascular mortality, while indicating a modest 15–17% reduction in the incidence of nonfatal MI in these cohorts.7–10
However, it seems very likely (or at least we have strong reason to hope) that the new evidence on specific sodium–glucose cotransporter-2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists will cause tight control of glucose to have a favorable effect on the reduction of macrovascular complications of type 2 diabetes.
The following is from Resource (1) below:
Implications of new evidence from cardiovascular
The major change from prior consensus reports is based on
new evidence that specific sodium–glucose cotransporter-2
(SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor
agonists improve cardiovascular outcomes, as well as secondary
outcomes such as HF and progression of renal disease,
in patients with established CVD or CKD. Therefore, an important early step in this new approach (Fig. 3) is to consider
the presence or absence of ASCVD, HF and CKD, conditions
in aggregate affecting 15–25% of the population with type 2
diabetes. While the new evidence supporting the use of particular medications in patients who also have established CVD or are at high risk of CVD is derived from large cardiovascular outcomes trials (CVOTs) demonstrating substantial benefits over 2–5 years, it is important to remember that each trial constitutes a single experiment. Within each drug class, results have been heterogeneous. It is not clear whether there are true drug class effects with different findings for individual medications due to differences in trial design and conduct, or whether there are real differences between medications within a drug class due to properties of the individual compounds. Where the current evidence is strongest for a specific medication within a class, it is noted. The ADA’s ‘Standards of medical care in diabetes’ will align with this document and will be updated to reflect new evidence as it emerges from ongoing clinical trials.
(1) Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [PubMed Abstract] [Full Text HTML] [Full Text PDF].
(2) Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Ann N Y Acad Sci. 2013 Apr;1281:36-50. doi: 10.1111/nyas.12044. Epub 2013 Feb 6.
(3) Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians [PubMed Abstract] [Full Text HTML] [Full Text PDF]. Ann Intern Med. 2018 Apr 17;168(8):569-576. doi: 10.7326/M17-0939. Epub 2018 Mar 6.
(4) Links To The Complete “Standards Of Medical Care In Diabetes – 2018” With Link To The Update And Additional Resources Posted on October 16, 2018 by Tom Wade MD.