Medicine

DIABETES MELLITUS

Diabetes Mellitus- group of metabolic, autoimmune diseases  Preceeded by abnormal glucose homeostasis
characterized by hyperglycemia resulting from defects in insulin a. Immune mediated
secretion, insulin action or both b. Idiopathic
Epidemiology: 2. Type 2 DM
 2013: 382M worldwide has DM  Insulin resistance
 Type 2 DM makes up 90%  Impaired insulin secretion
 Equal rates in men and women  Increased hepatic glucose production
Recommendtions for testing/ Risk factors:
1. Patients at age 45 yrs and above and, if normal, it
should be repeated at 3-year intervals
2. Younger age or be carried out more frequently in individuals
who:
 Obese (> 120% desirable body weight or a
BMI > 27 kg/m2)
 have a first-degree relative with diabetes
3. Testing should be considered at a younger age or be
carried out more frequently in individuals who:
 Members of a high-risk ethnic population
(e.g., African- American, Hispanic American,
Native American, Asian-American, Pacific
Islander)
 Delivered a baby weighing > 9 lb or have been
diagnosed with GDM
 Hypertensive (> 140/90)
 HDL cholesterol level < 35 mg/dl (0.90
mmol/l)
CRITERIA for DIAGNOSIS:
 and or a triglyceride level > 250 mg/dl (2.82 mmol/l)
Classification of DM
 Based on pathologic processes that lead to
hyperglycemia

SYMPTOMS OF DIABETES
 Polyuria, polydipsia and weight loss

PATHOPHYSIOLOGY:

Classification of Diabetes Mellitus

1. Type 1 DM
 b cell destruction usually leading to complete or near-
total insulin deficiency
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Katrina Pattaguan
 Medicine
DIABETES MELLITUS

become apparent and frank type 2 diabetes develops.IGT

may be defined as higher than normal blood glucose
levels, but not high enough to be called diabetes. People
with IGT may or may not go on to develop diabetes.
Glucose levels both before (fasting) and after (post-
prandial) meals increase steadily as the individual
progresses from normoglycemia to IGT and, finally, type
2 diabetes.

The progressive nature of type 2 diabetes

Mechanisms of insulin resistance

Type 2 DM
Genetic Considerations
 Type 2 DM has a strong genetic component
 Various genetic loci contribute to susceptibility, and
environmental factors (such as nutrition and physical
activity) further modulate phenotypic expression of the
disease.
 concordance of type 2 DM in identical twins is between
70 and 90%
 If both parents have type 2 DM, the risk approaches
40%

PATHOPHYSIOLOGY:
How do insulin resistance and b-cell dysfunction combine to Obesity
cause type 2 diabetes? Over time, changes in insulin resistance  Central or visceral location
and secretion lead to the onset of type 2 diabetes. In the early  Increase adipocyte mass leads to increase levels of
circulating free FA and fat cell products( nonesterified
stages, as insulin resistance rises, there is a compensatory
free FA, retinol binding protein 4, leptin, TNF, resistin
increase in insulin secretion and glucose levels remain normal and adiponectin which is a insulin sensitizing peptide
(normoglycemia).In the long term, however, as the b-cells  Increase FA insulin resistance
begin to fail, insulin secretion falls, IGT and hyperglycemia  Adiponectin is reduce in obesity
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Katrina Pattaguan
 Medicine
DIABETES MELLITUS

there is also increasing evidence that elevated free fatty acids

are toxic to the pancreas, in addition to promoting further
hepatic glucose output.
Impaired Insulin Secretion
 insulin secretion initially increases in response to CHRONIC COMPLICATIONS OF UNCONTROLLED DIABETES
insulin resistance to maintain normal glucose tolerance
 Eventually, the insulin secretory defect progresses to a  microvascular complications of both type 1 and type 2
state of grossly inadequate insulin secretion DM result from chronic hyperglycemia
 Beta cell mass is reduced by 50% in long standing  Macrovascular- Cerebral Cardiovascular, Peripheral
diabetes vascular
 Glucotoxicity and lipotoxicity  Microvascular- Retinopathy, neuropathy, nephropathy
 Large, randomized clinical trials of individuals with type
Increase hepatic glucose and lipid production 1 or type 2 DM have conclusively demonstrated that a
 insulin resistance in the liver reflects the failure of reduction in chronic hyperglycemia prevents or delays
hyperinsulinemia to suppress gluconeogenesis which retinopathy, neuropathy, and nephropathy
results in fasting hyperglycemia and decreased Diagnostics:
glycogen storage by the liver in the postprandial state -HBA1c: if >6.5 (If plasma glucose is consistently elevated,
 Insulin resistance in adipose tissue there is an increase in nonenzymatic glycation of
lipolysis and FA increase inc lipid synthesis in haemoglobin, glycemic history over the previous 2 to 3
hepatocytes non alcoholic fatty liver disease months, since erythrocytes have an average life span of
 Dyslipidemia in DM: elevated TG and small LDL;
120 days
reduced HDL
-FBS: >126 mg/dL
 Insulin resistance in adipocytes lipolysis and free
-OGTT: >200mg/dL
fatty acids flux increase lipid synthesis in liver
Also can test for lipid profile.
nonalcoholic fatty liver disease and dyslipidemia
Treatment Guidelines
Model of underlying factors in type 2 diabetes:
Goals of Therapy
insulin resistance and b-cell dysfunction
 eliminate symptoms related to hyperglycemia
 reduce or eliminate the long-term microvascular and
Pathophysiology of type 2 diabetes
macrovascular complications of DM
The consequences of insulin resistance at the tissue level
 allow the patient to achieve as normal a life-style as
include reduced
possible
insulin-dependent glucose uptake into liver, adipose tissue and
 eliminate symptoms related to hyperglycemia
muscle. Combined with excessive glucose production by the
 reduce or eliminate the long-term microvascular and
liver, this leads to hyperglycemia, which in turn causes a
macrovascular complications of DM
compensatory increase in insulin secretion. The b-cells of the
 allow the patient to achieve as normal a life-style as
pancreas are unable to sustain this increase in insulin secretion,
possible
thus the b-cells fail, and insulin secretion becomes defective (b-
cell dysfunction).In addition, excessive breakdown of
Targets for Lipids and BP in Type 2 Diabetes
triglycerides in the adipose tissue leads to increased circulating
Target
free fatty acids. This is particularly important since, not only do
LDL-C* <100 mg/dl (<2.6 mmol/l)
free fatty acids compete for glucose during metabolism, but
HDL-C >40 mg/dl (>1.1 mmol/l) for men
>50 mg/dl (>1.3 mmol/l) for women
TG^ <150 mg/dl (<1.7 mmol/l)
BP <130/<80 mm Hg
*In pts >40y/o with DM and TC ≥135mg/dl, without CVD, statin
therapy should be considered to achieve an LDL-C reduction of
30-40% regardless of baseline LDL-C levels. In very high risk
pts, eg, those with CVD and DM, an LDL-C goal of 70 mg/dl is an
option.
^NCEP ATP III guidelines suggest that in pts with TG ≥200mg/dl,
the non-HDL-C (TC minus HDL-C) level be used. The goal is
≤130 mg/dl.
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Katrina Pattaguan
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DIABETES MELLITUS

Treatment options for type 2 diabetes

 Sulfonylureas ex: Glipizide
 Glinides/meglitinides ex: Nateglinide
 Biguanides ex: Metformin
 Thiazolidinediones ex: Rosiglitazone
 -glucosidase inhibitors ex Acarbose

 Insulin
o Rapid- lispro aspart glulisine
o Short- regular
o Intermediate- NPH
o Long acting- detemir, glargine
 Fixed-dose oral antidiabetic
drug combinations
o e.g. glyburide/metformin,
glipizide/metformin,
rosiglitazone/metformin
 Other pharmacologic therapy – CV Risk Factors
o Hypertension – ACEI’s, ARB’s
o Dyslipidemia – Statins, Fibrates
o Aspirin

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Katrina Pattaguan