Diabetes mellitus (DM) comprises a group of common metabolic disorders that present
with hyperglycemia (elevated blood glucose).
• Defect in body energy regulation and utilization leading to multi-organ complications and
early mortality.
• Hyperglycemia is a cardinal manifestation due to insulin deficiency or insulin resistance.
• Several distinct types of DM exist and are caused by a complex interaction of genetics,
environmental factors and lifestyle choices.
• Depending on the etiology of DM, factors contributing to hyperglycemia may include
Reduced insulin secretion
Decreased glucose usage, and
Increased glucose production
• The metabolic dysregulation associated with DM causes secondary pathophysiologic
changes in multiple organ systems that impose a tremendous burden on the individual
with diabetes and on the health care system.
Classification of Diabetes Mellitus
• Recent changes in classification reflect an effort to classify DM on the basis of the
pathogenic process that leads to hyperglycemia, as opposed to criteria such as age of
onset or type of therapy.
• Two broad categories of DM are designated type 1(A & B) and type 2.
• Type 1A DM results from autoimmune beta cell destruction which usually leads to
insulin deficiency.
• Type 1B DM is also characterized by insulin deficiency as well as a tendency to develop
ketosis. The mechanisms leading to beta cell destruction in these patients are unknown.
• Type 2 DM is a heterogeneous group of disorders usually characterized by variable
degrees of insulin resistance, impaired insulin secretion, and increased glucose
production.
• The terms insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent
diabetes mellitus (NIDDM) are outdated because many individuals with type 2 DM
eventually require insulin treatment for control of glycemia, the use of the latter term
generated considerable confusion.
Risk Factors for Type 2 Diabetes Mellitus
• Family history of diabetes (i.e. parent or sibling with type 2 diabetes)
• Obesity i.e. body mass index (BMI) >27kg/m2
CMT 05211 Internal Medicine II NTA Level 5 Semester 2 Student Manual
Session 7: Diabetes Mellitus 84
• Age >45 years
• History of gestational diabetes mellitus
• Hypertension
• High density lipoprotein (HDL) cholesterol <0.90 mmol/l (35mg/dl)
• In HIV patients, the HAART therapy can increase risk of diabetes
Other Types of Diabetes Mellitus
• Other etiologies for DM include specific genetic defects in insulin secretion or action,
metabolic abnormalities that impair insulin secretion, and a host of conditions that impair
glucose tolerance.
Gestational Diabetes Mellitus (GDM)
• Glucose intolerance may develop and first become recognized during pregnancy.
Aetiology, Epidemiology and Pathogenesis of Diabetes Mellitus
Aetiological Classification of Diabetes Mellitus
• Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency)
Immune-mediated
Idiopathic
• Type 2 diabetes (may range from predominantly insulin resistance with relative insulin
deficiency to a predominantly insulin secretory defect with insulin resistance)
• Other specific causes of diabetes
Genetic defects of β-cell function
Genetic defects in insulin action
Diseases of the exocrine pancreas, pancreatitis, pancreatectomy, neoplasia, cystic
fibrosis, hemochromatosis, fibrocalculous pancreatopathy.
Endocrinopathies, acromegaly, cushing's syndrome, glucagonoma,
pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma
Drug- or chemical-induced, pentamidine, nicotinic acid, glucocorticoids, thyroid
hormone, diazoxide, β-adrenergic agonists, thiazides, phenytoin, protease inhibitors,
clozapine, beta blockers.
Infections, congenital rubella, cytomegalovirus, coxsackie.
Uncommon forms of immune-mediated diabetes’stiff-man’ syndrome, anti-insulin
receptor antibodies.
Other genetic syndromes sometimes associated with diabetes
Down's syndrome
Klinefelter's syndrome
Turner's syndrome
Wolfram's syndrome
Friedreich's ataxia
Huntington's chorea
Gestational diabetes mellitus (GDM)
Epidemiology of Diabetes Mellitus
• The worldwide prevalence of DM has risen dramatically over the past two decades.
• It is projected that the number of individuals with DM will continue to increase in the
near future.
• There is considerable geographic variation in the incidence of both type 1 and type 2
DM.
• The prevalence of type 2 DM and its harbinger, impaired glucose tolerance (IGT), is
highest in certain Pacific islands, intermediate in countries such as India and the United
States, and relatively low in Russia and China.
• This variability is likely due to both genetic and environmental factors. There is also
considerable variation in DM prevalence among different ethnic populations within a
given country.
Pathogenesis of DM
Type 1 DM
• Type 1A DM develops as a result of the synergistic effects of genetic, environmental, and
immunologic factors that ultimately destroy the pancreatic beta cells.
TYPE 2 DM
• Type 2 DM is a heterogeneous disorder with a complex etiology that develops in
response to genetic and environmental influences.
• Central to the development of type 2 DM are insulin resistance and abnormal insulin
secretion. Although controversy remains regarding the primary defect, most studies
support the view that insulin resistance precedes insulin secretory defects.
• Type 2 DM has a strong genetic component.
• Although the major genes that predispose to this disorder have yet to be identified, it is
clear that the disease is polygenic and multifactorial.
• The concordance of type 2 DM in identical twins is between 70 and 90%.
• Individuals with a parent with type 2 DM have an increased risk of diabetes if both
parents have type 2 DM the risk in offspring may reach 40%.
• Insulin resistance as demonstrated by reduced glucose utilization in skeletal muscle is
present in many non diabetic first-degree relatives of individuals with type 2 DM.
• However definition of the genetic abnormalities of type 2 DM remains a challenge
because the genetic defect in insulin secretion or action may not manifest itself unless an
environmental event or another genetic defect such as obesity is superimposed.
Metabolic Abnormalities Associated with Diabetes Mellitus
• Insulin Resistance
• Impaired Insulin Secretion
• Increased Hepatic Glucose Production
Clinical Features and Investigations
Clinical Features
• Possible clinical features of DM depend on the severity of disease and its complications.
These are listed below
Polyuria
Polydipsia
Polyphagia
Hyperglycaemia
Glycosuria
Ketosis, Acidosis
Coma
Weight loss
Fatigue
Weakness
Blurred vision
Frequent superficial infections e.g. vaginitis, fungal skin infections
Slow healing of skin lesions after minor trauma
• Metabolic derangements relate mostly to hyperglycemia (osmotic diuresis, reduced
glucose entry into muscle) and to the catabolic state of the patient (urinary loss of glucose
and calories, muscle breakdown due to protein degradation and decreased protein
synthesis).
• Blurred vision results from changes in the water content of the lens and resolves as the
hyperglycemia is controlled.
Investigations
• At primary health care facilities, the following can be done to patients suspected of
having DM.
Fasting blood sugar
Urine for sugar
Random blood sugar
this can be done using simple devices e.g. glucometers and urine dipsticks. When
DM is diagnosed, patients should be referred to hospitals for further investigations to
rule out complications and for initiation of the right medications.
Criteria for Diagnosis of Diabetes Mellitus
• Symptoms of diabetes plus random blood glucose concentration equal or greater than
11.1 mmol/L (200 mg/dl) or
• Fasting plasma glucose equal or greater than7.0 mmol/L (126 mg/dl)
• In the absence of unequivocal hyperglycemia and acute metabolic decompensation, these
criteria should be confirmed by repeat testing on a different day.
• Random is defined as without regard to time since last meal
• Fasting is defined as no caloric intake for at least 8 hours
• Glucose tolerance is classified into three categories based on the Fasting Plasma Glucose
(FPG)
FPG < 6.1 mmol/l (110 mg/dL) is considered normal
FPG 6.1 mmol/l (110 mg/dl) but < 7.0 mmol/l (126 mg/dl) is defined as impaired
Fasting Glucose (IFG)
FPG 7.0 mmol/l (126 mg/dl) warrants the diagnosis of DM
Treatment
• Treatment of DM should be initiated at hospital levels after thorough evaluation
including that of the complications. Thereafter, when patients are stable, follow up may
be done at health centres.
Overall Principles
• The goals of therapy for type 1 or type 2 DM are to
Eliminate symptoms related to hyperglycemia
Reduce or eliminate the long-term microvascular and macrovascular complications of
DM
Allow the patient to achieve as normal a life-style as possible
The care of an individual with either type 1 or type 2 DM requires a multidisciplinary
team
Central to the success of this team are the patient's participation, input and enthusiasm
all of which are essential for optimal diabetes management
Education for Patient with Diabetes Mellitus on Nutrition and Exercise
• Patient participation is an essential component of comprehensive diabetes care
• The patient with type 1 or type 2 DM should receive education about nutrition, exercise,
care of diabetes during illness and medications to lower the plasma glucose.
• Nutrition education should focus on balanced healthy eating (avoidance of alcohol, high
sugar foods such as desserts).
• Regular daily exercise is important, recommendation is 20-30 minutes of exercise daily
(this can be walking).
• Patients should also be educated as to the long term consequences of uncontrolled
diabetes (renal impairment, higher risk of ocular damage, increased risk of heart attack,
and neuropathy).
• Along with improved compliance patient education allows individuals with DM to
assume greater responsibility for their care.
• Patient education should be viewed as a continuing process with regular visits for
reinforcement; it should not be a process that is completed after one or two visits to a
nurse educator or nutritionist.
Monitoring Level of Glycemic Control
• Optimal monitoring of glycemic control involves plasma glucose measurements by the
patient and an assessment of long-term control by the physician measurement of
glycosylated haemoglobin (GHb ) and review of the patient's self-measurements of
plasma glucose.
• These measurements are complementary; the patient's measurements provide a picture of
short-term glycemic control whereas the GHb reflects average glycemic control over the
previous 2 to 3 months.
• Integration of both measurements provides an accurate assessment of the glycemic
control achieved.
Type I Diabetes Mellitus
Insulin Regimens
• In all regimens long-acting insulin (lente, ultralente, or glargine insulin) supply basal
insulin whereas prandial insulin is provided by either regular or lispro insulin.
• Lispro should be injected just before a meal.
• Regular insulin is given 30 to 45 min prior to a meal.
• No insulin regimen reproduces the precise insulin secretory pattern of the pancreatic islet.
• In general individuals with type 1 DM require 0.5 to 1.0 Unit/kg per day of insulin
divided into multiple doses.
• Initial insulin-dosing regimens should be conservative approximately 40 to 50% of the
insulin should be given as basal insulin to avoid hypoglycemia (which can be a serious
side effect of treatment of diabetes).
• A single daily injection of insulin is not appropriate therapy in type 1 DM.
• One commonly used regimen consists of twice-daily (2/3) injections of an intermediate
insulin (NPH or lente) mixed with a short-acting insulin before the morning and evening
meal.
• Such regimens usually prescribe two-thirds of the total daily insulin dose in the morning
(with about two-thirds given as intermediate-acting insulin and one-third as short-acting)
and one-third before the evening meal (with approximately one-half given as
intermediate-acting insulin and one-half as short-acting).
Type 2 Diabetes Mellitus
General Aspects
• The goals of therapy for type 2 DM are similar to those in type 1.
• While glycemic control tends to dominate the management of type 1 DM, the care of
individuals with type 2 DM must also include attention to the treatment of conditions
associated with type 2 DM (obesity, hypertension, dyslipidemia, cardiovascular disease)
and detection/management of DM-related complications.
• DM-specific complications may be present in up to 20 to 50% of individuals with newly
diagnosed type 2 DM.
• Reduction in cardiovascular risk is of paramount importance as this is the leading cause
of mortality in these individuals.
Glucose Lowering Agents
• Based on their mechanisms of action, oral glucose-lowering agents are subdivided into
agents that
Increase insulin secretion
Reduce glucose production or
Increase insulin sensitivity
• Oral glucose-lowering agents (with the exception of alpha-glucosidase inhibitors) are
ineffective in type 1 DM and should not be used for glucose management of severely ill
individuals with type 2 DM.
• Insulin is sometimes the initial glucose-lowering agent even in type 2 DM.
Oral Glucose Lowering Agents
• Insulin secretagogues
First generation sulfonylurea
Second generation sulfonylurea
• Biguanides (metformin)- this is usually the first drug of choice if available for type 2
diabetes as long as there are no contraindications (e.g., in renal failure).
• Thiazolidinediones - these are less favored for treatment given their recent complications
and side effects.
• Alpha-glucosidase inhibitors - also less effective as initial therapy.
Complications
Acute Complications
• Diabetic ketoacidosis (DKA) nonketotic hyperosmolar state (NKHS), Hypoglycemia are
acute complications of diabetes.
• DKA is seen primarily in individuals with type 1 DM, and NKHS is seen in individuals
with type 2 DM.
• Both disorders are associated with absolute or relative insulin deficiency, volume
depletion, and altered mental status.
• DKA and NKHS exist along a continuum of hyperglycemia, with or without ketosis.
• Both disorders are associated with potentially serious complications if not promptly
diagnosed and treated.
• Diabetic ketoacidosis is a medical emergency and if suspected needs immediate
intervention and transfer to the hospital
Chronic Complications of Diabetes Mellitus
• DM and its complications produce a wide range of symptoms and signs.
• Those secondary to acute hyperglycemia may occur at any stage of the disease.
• Those related to chronic complications begin to appear during the second decade of
hyperglycemia.
• Individuals with previously undetected type 2 DM may present with chronic
complications of DM at the time of diagnosis.
• The history and physical examination should assess for symptoms or signs of acute
hyperglycemia and should screen for the chronic complications and conditions associated
with DM.
• Chronic complications of DM affect many organ systems and are responsible for the
majority of morbidity and mortality associated with the disease.
• Chronic complications can be divided into vascular and nonvascular complications.
• The vascular complications of DM are further subdivided into
-Microvascular
Retinopathy
Neuropathy
Nephropathy
-Macrovascular Complications
Coronary Artery Disease
Peripheral Vascular disease leading to diabetic foot
Cerebrovascular disease
• Nonvascular complications include problems such as
Gastroparesis
Sexual dysfunction
Skin changes
• This division is rather arbitrary since it is likely that multiple pathogenic processes are
involved in all forms of complications.
• The risk of chronic complications increases as a function of the duration of
hyperglycemia.
• They usually become apparent in the second decade of hyperglycemia.
• Since type 2 DM may have a long asymptomatic period of hyperglycemia, many
individuals with type 2 DM have complications at the time of diagnosis.    
 
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