Therapy- Diabetes Overview

What is the equation for average blood glucose?

(A1C-2)*30

What is the annual rate of decline of β cell function in TD2M according to UKPDS?

10%

What is a normal glucose level in mmol/L?

5 mmol/L

Approximately what percentage of β cell function is lost at the time of T2DM diagnosis?

50-80%

What was the intensive control in DCCT?

A1C 6% or less

What was the intensive control for Action in Diabetes and Vascular DIsease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE)?

A1C 6.5% or less

What was the intensive control in ACCORD?

A1C <6%

Which intervention was used in STOP-NIDDM?

Acarbose 100mg TID

Which study looked at patients with CVD or two or more major CV risks factors and found that intensive glucose control increased mortality?

Action to Control CV Risk in Diabetes (ACCORD)

Which hormone is co-secreted with insulin from β cells in the pancreatic islets?

Amylin

What are physiological actions of insulin?

Carbohydrate/glucose metabolism, protein synthesis, lipid/free fatty acid uptake, and enzymatic activity

Why is T2DM considered progressive in nature?

Continued β cell decline decreases insulin production, and ultimately diagnosis and progression of diabetes if action is not taken

Which studies analyzed Type 1 Diabetes?

DCCT and EDIC

Which studies analyzed Intensive versus Standard Glycemic Goals on Microvascular Complications?

DCCT, EDIC, and UKPDS

What is the normal renal response to high glucose levels?

Decrease reabsorption of glucose

Which study found reduced development and occurrence of retinopathy (76%), microalbuminuria (39%), and neuropathy (60%)?

Diabetes Control and Complications Trial (DCCT)

Which interventions were the most beneficial in diabetes prevention studies?

Diet and exercise

Which diabetes prevention trial was stopped early because the intervention was far more beneficial than placebo?

Dream Trial

Which studies analyzed Intensive versus Standard Glycemic Goals on CV (macrovascular) Complications?

EDIC, UKPDS, ACCORD, ADVANCE, and VADT

Which study was a follow-up of DCCT and showed persistence of microvascular benefits?

Epidemiology of Diabetes Interventions and Complications (EDIC)

What is the ADA diagnostic criteria for an increased risk of diabetes aka Prediabetes?

FPG: 100-125 mg/dL, 2-hr OGTT: 140-199 mg/dL, HgbA1C: 5.7-6.4%

What are the ADA goals of therapy?

FPG: 80-130, PPG: <180, and A1C <7%

Which studies analyzed Prediabetes (diabetes prevention)?

Finnish Diabetes Prevention Study Group, Diabetes Prevention Project, Dream Trial, and STOP-NIDDM

Graph of the progressive nature of T2DM

Glucose levels begin to rise (impaired fasting glucose or impaired glucose tolerance) prior to diagnosis at which point some patients begin to develop microvascular complications

What are various "inputs" of glucose into blood vessels?

Gut (meals), Liver (produce, store, and release), and muscle (does not contribute directly to plasma glucose)

What is insulin resistance defined as?

Inability of a known quantity of insulin to increase glucose uptake and utilization in an individual as much as it does in a normal population

Which factors contribute to β cell failure in T2DM?

Incretin effect, Age, Genetics (TCF7L2), Amyloid (IAPP) deposition, Insulin resistance, Lipotoxicity FFA, and Glucose toxicity

What is T2DM defined as?

Insulin resistance in combination with a relative or absolute deficiency in insulin

What is the bottom-line evidence of intensive glycemic control studies (ACCORD, ADVANCE, VADT)?

Intensive glucose control was not better than standard glucose control in preventing CV complications in high risk patients, but there was benefit seen in microvascular complications

Diabetes Prevention Slide

KNOW: Especially when to use Metformin

The rate of glucose appearance into the blood is mainly from _____ or _____

Liver or meal

Which interventions were used in the Diabetes Prevention Project?

Metformin 850mg BID and 150 minutes of physical activity per week to achieve 7% weight loss

What is relative insulin deficiency?

Often hyperinsulinemic but have a degree of hyperinsulinemia inappropriately low for the prevailing glucose concentrations which leads to progressive loss of β cell function

What is the major physiological effect of increased endogenous insulin production in T2DM?

Overuse and death of β cells which ultimately leads to a decline in the production of endogenous insulin

What are the three classic symptoms of diabetes?

Polydipsia, polyphagia, and polyuria

How does the body compensate for insulin resistance?

Produces increased amounts of endogenous insulin

What are physiological actions of glucagon?

Promote gluconeogenesis and glycogenolysis in the liver

What is Ra?

Rate of glucose appearance into the blood

What is glucose disposal rate (Rd)?

Rate of glucose movement out of circulation

Which intervention was used in the Dream Trial?

Rosiglitazone 8mg QD

Which transporter is responsible for glucose reabsorption in the kidneys?

SGLT-2

What are physiological actions of amylin?

Slow gastric emptying, decrease glucagon secretion, and centrally (brain) stimulate satiety

Which drug class is known to induce diabetes?

Steroids

T/F: According to UKPDS, conventional and intensive therapy do not delay progression of β cell failure in T2DM but intensive therapy was more beneficial

True

T/F: GLP-1 deficiency occurs in T2DM

True

T/F: Patients begin to develop insulin resistance many years prior to the onset of T2DM

True

T/F: There is NOT currently an available therapy for regenerating β cells

True

What is the physiological difference between Type 1 and Type 2 Diabetes?

Type 1 is due to complete β cell destruction and Type 2 is due to insulin resistance

Which landmark study showed that intensive glucose control reduces microvascular complications?

United Kingdom Prospective Diabetes Study (UKPDS)

Which trial had an intensive control of absolute reduction of 1.5 percentage points in HbA1C as compared to standard therapy?

Veterans Affairs Diabetes Trial (VADT)

How can insulin resistance be improved in T2DM?

Weight loss and increased activity

Which cells produce and release glucagon?

α cells of pancreatic islets

Where is insulin released from?

β cells of pancreatic islets