Diabetes

Diabetes is one of the leading causes of death and disability in the world. It is estimated that there are up to 14 to 15 million people with Diabetes in the United States, and the healthcare costs increase every year. Diabetes is a group of metabolic disorders with one common manifestation: hyperglycemia. These disorders are associated with a high risk of development of complications for the eyes, kidneys, peripheral nerves, heart, and blood vessels.

• Abnormal glucose tolerance occurs in more than 60% of adults older than 60 years of age.

• A decrease in glucose tolerance results from decreased insulin sensitivity and impaired pancreatic beta-cell function.

• Because the population of the United States is aging and the prevalence of obesity increasing, the incidence of diabetes mellitus will continue to increase.

• The American Diabetes Association recommends that screening begin at age 45 and be repeated every 3 years (without known risks).

• Risk Factors: family history, obesity, hypertension, hypertriglyceridemia, impaired glucose tolerance.

Background

• In 1979 the National Diabetes Data Group established a classification scheme of IDDM and NIDDM

• The oral glucose tolerance test was established as the preferred diagnostic test

New Classification

• type 1

• type 2

• other secondary types

• gestational

Diagnostic Criteria

• symptoms plus:• 2 abnormal fasting plasma glucose levels >

126 mg/dl, or• 2 two-hour post-prandial plasma glucose

levels > 200 mg/dl after a 75 gm load, or• 2 “casual” glucose readings of > 200, or• a combination of any 2 abnormal values

– [fasting is preferred as it predicts complications]

Gestational Diabetes

• GDM develops in 1-3% of all pregnancies.

• Women with GDM are characterized by a relatively diminished insulin secretion coupled with a pregnancy-induced insulin resistance primary located in skeletal muscle tissue.

• Glucose tolerance returns to normal postpartum in the majority of women with GDM.

• Women with previous GDM have a high risk of

developing overt diabetes mellitus later in life.

Metabolic Syndrome

• glucose intolerance

• hypertriglyceridemia

• low HDL

• hypertension

• central obesity

• accelerated atherosclerosis

DCCT Results

• 50-75% decreased risk of retinopathy, nephropathy, and neuropathy with intensive insulin therapy

• Reduced hba1c from 9.0 to 7.2 % (nl 4-6)

• 3-fold increased risk of hypoglycemia

UKPDS

• Improved b.s. control reduces the risk of retinopathy and nephropathy and possibly neuropathy.

• 35% reduction in microvascular complications for each 1% decr. in HbA1C

• 16% reduction in CVD mortality & morbidity (non-significant)

• Supported aggressive BP control

Goals of Treatment

• Prevention of Acute Decompensation: – DKA or Hyperosmolar hyperglycemic

nonketotic syndrome

• Alleviation of Symptoms:– blurry vision, polyuria, polydipsia, abdominal

pain, fatigue, weight loss, infections

• Prevention of chronic complications:– retinopathy, nephropathy, PVD, CVD, HL

Management Plan

• Emphasize self-management• Set short and long term goals• Appropriate use of medications• Individualized nutritional instruction• Lifestyle changes (exercise and smoking)• Patient and Family Education• Monitoring instructions• Annual eye exams• Appropriate medical follow-up• Dental hygiene

Diabetes & CVD

• Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients

• myocardial infarction is responsible for 20% of deaths of in diabetic subjects

• re-infarction and heart failure are more common in diabetics

• diabetes mellitus increases cardiovascular mortality and morbidity in hypertensive patients

DM in the Elderly

• Elderly lean subjects have impaired glucose-induced insulin release

• some lean subjects have islet cell antibodies

• obese elderly subjects have insulin resistance

Sulfonylureas

• stimulate insulin secretion

• most commonly used class of drugs

• bind to ATP-dependant potassium channel

• may reduce intra-cellular K+ levels in vascular smooth muscle cells

• tolbutamide associated with adverse cardiovascular outcomes in UGDP

First Generation Sulfonylureas

Acetohexamide 500-750 mg/d $14.18

Chlorpropramide

250-375 mg/d $1.19

Tolazemide 250-500 mg/d $ 2.81

Tolbutamide 1000-2000 mg/d $ 2.75

Second Generation Sulfonylureas

Amaryl Glimepiride

1-4 mg $ 7.06

Glucotrol Glipizide* 10-20 mg $ 21.38

GlucotrolXL

Glipizide 5 mg $ 10.07

DiaBeta Glyburide**

$ 20.43

Micronase Glyburide 3-12 mg $ 22.93

Glynase Glyburide $ 20.10

Thiazolidinedione

• troglitazone

• insulin sensitizer

• better control of glycemic parameters

• lipid lowering activity

• 20-30% of diabetics do not respond

• liver toxicity in 2% of patients

• newer agents in development

Biguanides

• Phenformin: assoc. w/ incr risk of lactic acidosis

• Metformin• decr insulin resistance• incr insulin mediated glucose uptake• decr hepatic lipolysis• reducing gluconeogenesis • contraindicated in renal or hepatic disease

Acarbose• inhibits alpha-glucosidases in the small intestine• delays the digestion and absorption of complex

carbohydrates• smaller rise in postprandial plasma glucose levels • greater effectiveness in controlling postprandial

hyperglycemia• can potentiate the hypoglycemic effects of

sulfonylureas or insulin• Gastrointestinal adverse effects are common • overall decrease in the glycosylated hemoglobin

by 0.5-1.0%

Lispro (Humalog)

• the first human insulin analogue to be approved in the United States.

Aldose Reductase Inhibitors

• decr flux through the polyol pathway

• decr sorbitol levels

• under study as inhibitors of neuropathy

Supplements Use

• Low serum ascorbate levels have been documented in patients with DM.

• Ascorbic acid supplements improve glycemic control and decrease FBS, TG, & cholesterol.

• AA supplements reduce sorbitol accumulation.

• Up to 1 gm/d is recommended as higher doses may blunt the insulin response to glucose.

Supplements 2

• Supplemental Vit E reduces the oxidation of LDL cholesterol.

• Pyridoxine has been used to forstall the onset of diabetic neuropathy.

• Magnesium deficiency is associated with increased vascular disease in DM & HT.

• Niacinamide may reduce Beta cell destruction in Type 1 DM.

Supplements 3

• Chromium: still controversial. No impact on non-chromium deficient elderly subjects.

• Some patients respond with reduced hypertriglyceridemia

• GTF chromium rather than metal ion: brewer’s yeast, chromium picolinate or chromium nicotinate.

Supplements 4

• Vitamin’s C and E improve insulin action and metabolic control.

• Mg supplements enhance glucose-induced insulim release and insulin-mediated glucose disposal.

• Vanadium is currently being evaluated• gamma-linolenic acid may reduce the

progression of neuropathy

Type 1 DM and Vit A

• Recent studies have shown decreased serum levels of Vit A in type 1 but not type 2 patients.

• This is probably a result of reduced RBP as insulin fixes this problem and Vit A supplements don’t.

• Vit A supplements in type 1 patients should be avoided to prevent hepatotoxicity