Pathophysiologic Basis of Treatment of type 2 Diabetes

Pathophysiologic Basis of Treatment of type 2 Diabetes

By Dr.V.K.Gujral
Consultant Diabetologist,
New Delhi.

The primary goals of managing type 2 diabetes are to

  • Eliminate symptoms of hyperglycemia
  • Achieve and maintain normal or near normal metabolic and metabolis parameters (both fasting & postprandial blood glucose levels glycated Hb,Fasting LDL and HDL Cholesterol and Triglycerides)
  • Assist the patient in achieving and maintaning a reasonable body weight
  • Prevent or delay the development and progression of microvascular and macrovascular complications.

Therapeutic efforts to achieve these goals involve using a variety of treatment modalities

  • Dietary Modifications
  • Regular physical activity
  • Oral Antidiabetic agents
  • Insulin

An individualised approach is recommended based on

  • Patient age
  • Presence of coexisting disease and /or diabetes related complications
  • Lifestyle , including - .Attitudes .Habits .Cultural / Ethnic status
  • Financial considerations
  • Ability to learn and follow self - management skills
  • Level of patient motivation

The cornerstone of effective diabetes management is maintaining good glycemic control.Compelling evidence indicates that long term glycemic control can prevent or delay the development of complications .The DCCT Trial demonstrated definitely the value of intensive therapy of Type 1 Diabetes in delaing the onset and progression of microvascular complications of diabetes . The UKPDS demonstrated the same for the type 2 Diabetes.

It is likely that no single genetic defect willemerge to explain type 2 diabetes , thus the disease is heterogenous and possibly multigenetic , and likely has a complex etiology.Even though the disease is genetically heterogenous, there appears to be a fairly consistent phenotype once the disease is fully menifested. Most patients with type 2 diabetes and fasting hyperglycemia are characterised by:

  • Insulin Resistance
  • Impaired Insulin Secretion
  • Increased Hepatic glucose production

Although these metabolic abnormalities have been well studied ,the etiologic sequence has only recently come into focus.It is clear that the increased hepatic glucose production of type 2 diabetes is secondary and can be fully researved with a variety of antidiabetic treatment options.

The proposed etiological sequence is that insulin resistance is manifested initially , leading to increased insulin secretion to maintain the compensated IGT state .Later the compensation fails and beta cell functon declines ,leading to hyperglycemia .In addition , the conversion of IGT to type 2 diabetes can be influenced by:

  • Ethnicity
  • Degree of obesity
  • Distribution of body fat
  • Sedentary lifestyle
  • Ageing

Considerations For Choice Of OHA

  • Age
  • Weight
  • Duration of diabetes
  • Presence of Dyslipidemia
  • Severity of hyperglycemia
  • Presence & degree of Renal / Hepatic Disease
  • Ulcer or other GI problem

Obese patient with recent diabetes with / without Dyslipidemia

  • Metformin / Rosi / Pioglitazone
  • Acarbose
  • Sulfonylurea - only if signs of glucotoxicity

Thin Elderly patient

  • Acarbose
  • Repaglinide
  • Glitazones (if Normal Hepatic functions)

Acceptable FBG but high HbA1c

  • Acarbose
  • Repaglinide
  • Metformin

Non Obese (lean) Type 2 DM

  • Glibenclamide
  • Glipizide
  • Glimipiride
  • Insulin

Prolonged, Severe Hyper Glycemia

  • Short term insulin, then OHA
  • Any SU + Glitazone + Metformin

Severe Renal / Hepatic Dysfunction

  • Repaglinide
  • Acarbose
  • Insulin

Taking patients with type 2 diabetes Off Insulin

You may be successful if:
  • Duration < 10 Years
  • Obese Persons
  • FBg > 200 and PPBG < 250
  • Diabetes diagnosed after 35: add & Substitute - Glitazones + Metformin + Acarbose + ? Repaglinide / Glimipiridey