Glucose control

Several studies reveal intensive glucose control in type 2 diabetes reduces progression of micro vascular disease (The Diabetes Control and Complications Trial Research Group).

Effect of intensive glucose control in patients with type 2 diabetes on macro vascular complications is uncertain as studies are not consistent.

Glycemic control his failed to consistently reduce the risk for macrovascular complications and overall mortality.

Glycemic variability leads to both microvascular and macrovascular complications  in patients  with type two diabetes: two patients can have the same hemoglobin A-1 C level but glucose readings may be more widely variable around the average glucose level and those with higher variability have a greater risk for complications than patients with less variability.

In randomized trials with intensive glycemic control has not resulted in lower risk of lmajor cardiovascular events or a death than standard glycemic control among patients with type one and type two diabetes during intervention periods: extended trials may indicate cardiovascular benefits.

Lifestyle intervention is a major point for the prevention and management of type two diabetes as highlighted by the reduction in incident diabetes in patients receiving lifestyle interventions.

Once type two diabetes is diagnosed the effect of lifestyle intervention, particularly on cardiovascular outcomes, is less established.

The Look AHEAD trial randomizing obese patients with type two diabetes, with and without prior cardiovascular disease to intensive weight loss lifestyle intervention with standard care with the goal of reducing body weight in improving long-term cardiovascular outcomes: weight and waist circumference losses and control was significantly improved in the intensive treatment group compared with standard treatment, the cardiovascular event rate reduction did not reach statistical significance, after nearly 10years follow-up

The Action in Diabetes and Vascular Disease (ADVANCE) trial and the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial reported no significant decreases in cardiovascular events with intensive glucose management.

ACCORD trial randomly assigned patients with type 2 diabetes and cardiovascular disease received intensive therapy, Hgb A1C target <6.0 or standard therapy Hgb A1C 7-7.9-follow up after termination of the study at 5 years revealed reduced nonfatal myocardial infarctions but increased 5 year mortality (ACCORD Study Group).

In the ACCORD trial, and in the ADVANCE trial, and in the veterans Affars Diabetes Trial (DDDT) have shown that no cardiovascular benefit is associated with tight control of glycemia: with the hemoglobin A-1 C of 6.4%, 6.4%, and 6.9% for the ACCORD, ADVANCE, and VADT, respectively compared with control arms of 7.5%, 7%, and 8.4%, respectively.

In the ACCORD study an increased mortality in the intensive control group prematurely closed the study.

An increase in mortality was not found in ADVANCE or VADT study.

In the VADT study 5.6 years of intensive glucose control resulted at a 15 year analysis of no lowering in the risk of cardiovascular events than those who had receive standard therapy only during the period of investigation.

The VADT study included 1791 military veterans with type 2 diabetes with mean followed 11.5 years who were randomly assigned to intensive or standard control for a medium and a 5.6 years: the group difference of 1.5 percentage points in the median glycated hemoglobin levels were 6.9% in the intensive therapy group versus 8.4% in the standard care group.

In the VADT 15 year follow up study older patients with advanced diabetes should not expect cardiovascular benefits from intensive glycemic control: interventions that reduce cardiovascular risk such as smoking sensation, blood pressure control, statin therapy, use of antiplatelet agents, and the use of glucose lowering agents with proven cardiovascular benefits with establish cardiovascular disease should be prioritized.

Yet, there was no significant differences between the groups in the incidence of cardiovascular events, cardiovascular mortality, or all-cause mortality.

At the 10 year interim analysis the intensive therapy group had a significant lower incidence of cardiovascular events than the standard therapy group.

Severe hypoglycemia was seen in the intensive control groups in all three studies.

While glucose control may reduce micro vascular complications, blood pressure control has a greater effect.

A number of studies have shown that in spite of successful glucose control there is no benefit in terms of major cardiac events or most of the microvascular disease end points examined.

Glycemic fluctuations and postprandial glucose excursion are associated with the presence and severity of coronary aryery disease in patients with type two diabetes.

Glycemic fluctuations may be associated with diabetic peripheral neuropathy, cardiovascular autonomic neuropathy, and gray matter atrophy in the limbic and central autonomic systems.

The United Kingdom Prospective Diabetes Study (UKPDS) revealed no significant improvement in the rate of myocardial infarction in newly diagnosed patients.

The United Kivadtngdom perspective diabetes study did show reductions in the risk of cardiovascular events in death among patients with newly diagnosed type two diabetes who have received intensive glycemic control.

The Diabetes Control and complications trial (DCCT) did not show significant decrease in cardiovascular events with intensive control in young patients with type 1 diabetes, but a follow-up study the Epidemiology of Diabetes Interventions and Complications (EDIC) trial did indicate a delayed benefit at 10 years with fewer cardiovascular events in the intensive study group.

Glycemic control is suboptimal in the majority of adolescents and young adults with type one diabetes with only about 17% attaining hemoglobin A1C target of less than 7.5% and 14% contained in the target of less than 7%.

Circumstantial evidence for tight control in the ICU seems compelling and glucose can be seen as a marker of the function of overall metabolism and the anabolic effects of insulin.

Blood glucose concentrations on admission, during a postoperative period, or the mean glucose concentration in the hospitalized patient are directly related to adverse outcomes including prolonged hospital stay, readmission and mortality.

Elevated glucose levels at the time of severe illness are associated with worse long-term outcomes such as risk from death, and congestive heart failure at 1 year after myocardial infarction or degree of disability after stroke.

Efforts to control blood sugar levels after cardiac surgery markedly reduces sternal wound infections compared to historical control (Funary).

Strict glycemic control blood sugar 81 to 108 mg/dL is associated with more deaths compared with conventional goals of less than 180 mg/deciliter in the intensive care unit and the acute care environment.

The Diabetes Insulin Glucose in Acute Myocardinal Infarction (DIGAMI) study randomly compared intravenous insulin followed by multiple dose insulin therapy vs. standard care for patients with diabetes and acute myocardial infarction: control of blood glucose from the time of admission to the post discharge period reduced mortality at 1 year by 26% (Malberg).

The National Committee for Quality Insurance Health care Effectiveness Data and Information Set (HEDIS) suggests hemoglobin A-1 C Gold to listen 7% for persons younger than 65 years of age without cardiovascular disease or in stage complications and diabetes and establish the new goal of less than 8% for persons 65 to 74 years of age.

A randomized controlled trial of 700 pediatric ICU patients revealed type goes control with insulin infusion targeting age-adjusted normal glycemia prevented serious ICU morbidity compared with usual care(Vlasselaers D et al).

In the above study the number of patients with new infections was reduced with tight glucose control, there was less inflammation, less myocardial damage, shorter duration of hemodynamic support and shorter stays in the ICU.

The incidence of hypoglycemia of 40 mg/dL or lower increased from 1% with usual care to 25% with tight glucose control (Brown TC et al).

Symptomatic hypoglycemia in young children is associated with variable brain damage with diffuse white matter injury, hemorrhage, infarction, basal ganglia/thalamic abnormalities, and cortical lesions(Burns CM et al).

In critically ill patients on IV insulin, glucose levels should be maintained between 140 and 180 mg/dL.

For non-critical patients on subcutaneous insulin premeal glucose targets should be less than 140 mg/dL, in conjunction with random glucose targets of less than 180 mg/dL.

Tight glycemic control doesn’t reduce mortality or major cardiovascular events in long-term follow-up.(Advance On trial).

Tight control doesn’t do any harm  and prevents serious renal complications.

Above study shows no effect on the rate of death from renal disease, nor were there any reductions in serious eye complications.

Im the Glycemia Reduction in Type 2 Diabetes – Glycemic Outcomes study, type two diabetics who were receiving metformin were randomly assigned to receive insulin Glarine, the sulfonylurea glimepiride, the glucagon-like peptide –1 receptor agonist liraglutide or sitagliptin, a dipeptyl peptidase 4 inhibitor: all four medication‘s when added to metformin decreased glycated hemoglobin levels.

Glarine and  liraglutide was significantly, although modestly, more effective in achieving and maintaining target glycated hemoglobin levels.

In the above study the incidences of microvascular complications and death were not materially different among the four treatment groups: there was possible differences among the groups in the incidence of cardiovascular disease.

Adding once weekly, tirzpatide versus prandial insulin in basal insulin  treated patients with type two diabetes and inadequate glycemic control results in the greater reduction, hemoglobin A1c, along with more weight loss in less hypoglycemia.


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