Diabetes mellitus Types,Causes,Symptoms and Diagnosis

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

Diabetes mellitus Types,Causes,Symptoms and Diagnosis

Diabetes mellitus is of two types according to etiology:

 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.