Diabetes mellitus Overview Types Causes,Symptoms with Diagnosis

Diabetes mellitus is a group of metabolic disorders with hyperglycemia.

Glucose intolerance is characterized by hyperglycemia resulting from defects in glucose and fat metabolism. Overt diabetes is classified as type 1 (T1DM), type 2 (T2DM), and gestational (GDM) A chronic metabolic disorder marked by hyperglycemia. Diabetes mellitus (DM) results either from failure of the pancreas to produce insulin (type 1 DM) or from insulin resistance, with inadequate insulin secretion to sustain normal metabolism (type 2 DM).

Hyper glycemia is due to :

• · Decreased insulin secretion
• · Decreased glucose usage
• · Increased production of glucose.
• Hyperglycemia and associated metabolic disturbances causes involvement of multiple organ systems lead­ing to morbidity and mortality.

Diabetes mellitus Types,Causes,Symptoms and Diagnosis

 TYPE I DIABETES:

• Type 1: There is absolute insulin deficiency or defective insulin secretion.
• There is pancreatic Beta cell destruction lead­ing to absolute insulin deficiency.
• Type I occurs usually at less than 30 years age.
• Type I A diabetes –
• Immune mediated­Auto immune beta cell destruction leading to insulin deficiency.
• Type I B diabetes
• Idiopathic insulin deficiency Tendency to ketosis
• – No immunologic marker
• – Cause unknown
• Common in Asians.

TYPE 2 DIABETES

• There is insulin resistance, insulin deficiency, and defect of insulin secretion.
• Type 2 is
• · Due to insulin resistance
• · Impaired insulin secretion
• · Increased glucose production
• · There is genetic and metabolic defect lead­ing to hyperglycemia.

Two terms: Insulin dependent diabetes mellitus (IDDM or type 1) and Non Insulin dependent diabe­tes mellitus (NIDDM or type 2) are now not used as NIDDM may also require insulin later in life. In obese adolescents type 2 diabetes mellitus may be seen.

Ill. OTHERS

• A. Genetically defined, monogenic form of DM MODY-maturity onset diabetes of the young
• · 5 different variants of MODY
• · Mutation in genes encoding islet tran­scriptase factors
• · Autosomal dominant disorders
• · Homozygous mutation causes severe neonatal diabetes.
• Genetic defects of beta cells due to muta­tions- Maturity onset diabetes of the young called MODY is a subtype of diabetes mellitus which is autosomal dominant, early on­set hyperglycemia, with impaired insulin se­cretion.
• • MODY I – MODY 6
• B. Genetic defect in the action of insulin.
• · Type A – Insulin resistance
  • · Leprechaunismb
  • · Rabson-Mendenhall syndrome
  • · Lipodystrophy.
• C. Diseases of pancreas
• D. Endocrinopathies
  • · Acromegaly
  • · Cushing’s syndrome
  • · Pheochromocytoma
  • · Hyperthyroidism
  • · Glucagonoma.
• E. Drug induced
  • · Thyroid hormones
  • · Beta agonists
  • · Thiazides
  • · Phenytoin
  • · Beta blockers.
• F. Infections
• G. Anti-insulin receptor antibodies
• H. Genetic syndromes
  • · Down’s syndromes
  • · Klinefelter’s syndrome
  • · Turner’s syndrome
  • · Friedreich’s ataxia
  • · Myotonic dystrophy
  • · Huntington’s chorea.

IV. GESTATIONAL DIABETES MELLITUS

• Occurs in pregnant females due to insulin resis­tance related to metabolic changes in later preg­nancy.
• Reverts to normal usually. Seen in 4% of pregnancies.
• May develop into diabetes mellitus later in life 60%).

Signs and Symptoms

History

• Characteristics of the onset of disease (e.g., DKA, routine lab evaluation)
• Diet and exercise history

History of diabetes-related complications:

• Microvascular: Eye, kidney, nerve
• Macrovascular: Cardiac, cardiovascular disease, peripheral artery disease
• Other: Sexual dysfunction, gastroparesis
• Tobacco and alcohol use
• Polyuria
• Polydipsia
• Unexplained weight loss (sometimes accompanied by polyphagia)
• Blurred vision

Physical Exam

• Blood pressure, including orthostatics
• Dorsalis pedis and posterior tibialis pulses
• Funduscopic exam
• Thyroid palpation
• Skin exam (for acanthosis nigricans and insulin injection sites), trophic changes on toes
• Neurological exam:
• ›Patellar and achilles reflexes
• ›Proprioception, vibration, and monofilament sensation tests

Diagnostic Tests & Interpretation

Normal glucose tolerance

• FPG (Fasting plasma glucose) mg/dl   normal tolerance ( <110)   impaired fasting glucose tolerance (110-125)  —
• 2hPG (2h plasma glucose) (glutose load 75g)
• RBG (Random)
• Normal glucose tolerance test
• FPG – Fasting plasma glucose (no calorie intake in past 8 hrs).
• RBG (Random) any time irrespective of last meal (~ 200 mg/dl in DM).
• HbA1c as a diagnosis test for diabetes mellitus is not standardized.

Prediabetes :

• Categorized as IFG when diagnosed using a fasting plasma glucose (FPG) or IGT when diagnosed using the oral glucose tolerance test (OGTT):
• IFG: FPG 100 mg/dL and <126 mg/dL
• IGT: A 2-hour plasma glucose between 140 mg/dL and 199 mg/dL following ingestion of a 75-g glucose load

Diabetes :

• Diagnosed using any one of the following 3 tests, each of which must be confirmed on a subsequent day. A1C should not be used to diagnose diabetes
• FPG: Preferred test, FPG 126 mg/dL
• Casual plasma glucose (CPG) and symptoms of diabetes. CPG is measured at any time of day, regardless of time since last meal. CPG 200 mg/dL accompanied by
• Criteria for Diagnosis of Diabetes Mellitus

For screening of diabetes mellitus

symptoms is diagnostic

• OGTT: More sensitive and specific than FPG, but poorly reproducible; not recommended for routine clinical use. A 2-hour plasma glucose 200 mg/dL following ingestion of a 75-g glucose load is diagnostic
• Type 2 – FPG is done because patient may have type 2 diabetes mellitus for 10 yrs before being diag­nosed.
• 50% of patients of type – 2 diabetes mellitus have one or more complications at the time of diagnosis.
• Type I diabetes mellitus is usually symptomatic from the onset itself.
• Type I diabetes mellitus there are immunological markers.
• The likelihood of type 2 diabetes mellitus is more in the following:
• · Family history of diabetes (parents and sibling with type 2 diabetes mellitus)
• · Obesity ~ 20% desired body weight
• Age> 45 yrs
• Race – Asian, Africans
• Impaired fasting glucose (IFG) or Impaired glu­cose tolerance (IGT)
• H/o gestational diabetes mellitus or baby’s weight more than 9 pounds
• BP > 140/90 mmHg
• HDL < 35 mg/dl or TG > 250 mg/dl Polycystic ovarian syndome (POD).

PATHOGENESIS Insulin

• Insulin is produced by beta cells of pancreas. Glucose levels of less than 70 mg/dl stimulate synthesis of insulin.
• Meals and other stimuli cause release of insulin in bursts every 10 minutes or so and lasting upto 3 hours.
• Impaired fasting glucose or Diabetes Mellitus Impaired glucose tolerance
• Type 1 A diabetes mellitus – Pancreatic beta cells are destroyed due to genetic, environmental and immu­nologic factors.
• The destructive process is progressive.
• When 80% beta cells are destroyed overt diabetes appears.
• When there is increased insulin requirement as dur­ing puberty or infection overt diabetes occurs.
• There is a honeymoon period when without insulin blood sugar is controlled due to reduced insulin re­quirement. Gradually all the beta cells are destroyed by autoimmune process and there is complete .insulin deficiency leading to diabetes.

Genetic considerations

• Type 1 A diabetes mellitus involves multiple genes.
• Type 1 A – concordance in twins is 30 – 70%.
• Most have HLA DR3 or DR4 haplotype.
• But most persons with HLA DR-3 or DR-4 do not have diabetes.
• Most with type lA diabetes mellitus do have a first degree relative with this disorder.
• B. In type 2 diabetes mellitus there is strong genetic component. Disease is polygenic and multifactorial.
• Insulitis – Pancreatic islets are infiltrated with Iym­phocytes.

Immunologic Markers

• Islet cells antibodies are present in majority of indi­viduals (more than 75%) with new onset type 1 A diabetes mellitus, in a minority of individuals with type 2 diabetesmellitus and occasionally (5%) in individu­als with gestational diabetes mellitus.

Environmental factors –

• Viruses-Coxsackie and Rubella, and bovine milk intake (proteins) may cause type 1 A.
• Prevention of type I
• · By administration of insulin to induce immune tolerance
• · Immunosuppression
• · Selective T cell subset deletion
• · Induction of tolerance to islet proteins
• · Blocking cytotoxic cytokines
• · Increase islet resistance.