Types of Diabetes Mellitus

  • Created by: MazzaW
  • Created on: 18-11-19 17:56

Type 1 Diabetes Mellitus

Autoimmune destruction of pancreatic beta cells.

Presents in preschoolers and teenagers. Does not present under 6 months old. Genetic risk- more likely to be passed on by fathers, HLA on chr 6 responsible for 50% genetic risk. 

Sx: polydipsia, polyuria, wt loss, fatigue, DKA

Dx: clinical- usually have 1+ of hyperglycaemia, ketosis, rapid wt loss, PMH/FH of autoimmunity, BMI<25, age of onset <50, insulin dependent

Ix: C-peptide good marker of pre-hepatic insulin secretion (better discriminative value the longer it is done after Dx), islet Abs. If diagnostic uncertainty: GAD Ab, IA-2 Ab, ICA (islet cell autoAb)

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Type 2 Diabetes Mellitus

RFs: FH, obesity, metabolic syndrome, sedentary lifestyle, Afro-Caribbean, Hx of gestational diabetes, PCOS, socioeconomic factors (higher risk in urban areas)

Peripheral insulin resistance + relative insulin deficiency (decreased beta cell function). Caused by fat accumulation in liver and pancreas. 

Clinical Dx PLUS: random plasma glucose >11mmol/L OR fasting plasma glucose >7mmol/L OR HbA1c>48mmol/mol

If no Sx, need 2 confirmatory tests.

Don't use HbA1c if: young, acutely unwell, recently started drugs that may cause rapid changes in glucose, haemolytic anaemia, haemoglobinopathy, acute pancreatic damage, HIV, renal failure

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Glucokinase MODY

Most common form of MODY in children, 30% of all UK MODY cases.

Pathophysiology: insulin secretion remains regulated but there is a higher threshold for glucose-stimulated insulin secretion. Microvascular complications not observed.

Presentation: incidental hyperglycaemia in children, common in gestational diabetes, residual insulin secretion at least 3 yrs after Dx of T1DM or lack of metabolic syndrome in those presumed to have T2DM

Clinical features: persistent raised fasting glucose, no extrapancreatic features, usually non-obese, often asymptomatic

Mgmt: do not use pharmacological intervention, stop any glucose-lowering treatment, consider testing parents/family to support Dx

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Transcription factor MODY: HNF-1a and HNF-4a

HNF-1a MODY = most common form of MODY

Clinical picture: normoglycaemic in childhood, typically develop DM aged 12-30, worsening glycaemia with age, often misdiagnosed as T1DM, poor control does lead to complications

May have FH of DM. 

Mgmt: v sensitive to low dose sulphonylureas so these are 1st line (gliclazide, glibenclamide), can also use prandial secretagogues. Stop insulin if it was previously prescribed after misdiagnosis as T1DM.

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Transcription factor MODY: HNF-1b

HNF-1b is closely related to HNF-1a but causes a distinct DM phenotype with pancreatic and genitourinary anomalies. Causes 5-10% MODY in the UK.

Clinical features: RCAD (renal cysts and diabetes syndrome), renal function variable (can be mild, 50% require RRT), DM alone unusual

Mgmt: pts not sensitive to sulphonylureas, usually require insulin

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Gestational diabetes

Who is offered screening? BMI > 30, previous macrosomic baby (>4.5kg), previous GDM, FH of diabetes, from an ethnic minority known to be at higher risk

Screening test: OGTT

Criteria for Dx: fasting glucose >5.6 or plasma glucose (after 2hrs) > 7.8

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Neonatal diabetes

Very rare.

Presentation: birth-6months, high glucose levels or DKA, low birth weight, very low C-peptide (low insulin release), DM may be transient or permanent, some subgroups have neurological involvement

Mechanism: 50% have mutation of K ATPase channel of beta cell, so no beta cell depolarisation and failure of insulin release

Mgmt: may respond to sulphonylurea therapy

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Endocrinopathies causing diabetes

Cushing's syndrome: inhibition of insulin sensitivity (liver and muscle), stimulation of hepatic gluconeogenesis

Hyperthyroidism: increased hepatic gluconeogenesis, rapid GI glucose absorption

Acromegaly: stimulates gluconeogenesis and lipolysis, hepatic and muscle insulin resistance leading to hyperinsulinaemia

Phaeochromocytoma: inhibition of pancreatic insulin release, stimulation of hepatic gluconeogenesis

Glucagonoma: hepatic gluconeogenesis

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Genetic syndromes linked to diabetes

Down's syndrome: autoimmunity (main factor)

DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, Deafness) AKA Wolfram's syndrome: AR inheritance of mutation in WFS1, reduced insulin production

Turner's syndrome: autoimmune T1DM

Prader Willi syndrome: obesity, insatiable craving for food

Lawrence-Moon and Bardet-Biedl syndromes: obesity, insulin resistance

Klinefelter's syndrome: high truncal fat, insulin resistance

Myotonic dystrophy: insulin resistance

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Insulin resistance syndromes

Clinical features: persistent hyperglycaemia despite large doses of insulin, acanthosis nigricans, polycystic ovary syndrome

Genetic causes:

  • insulin receptor defects (loss of function mutations): cause a range of resistance, includes Donahue syndrome and Rabsen-Mendenhall syndrome
  • lipodystrophy syndromes
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Lipodystrophy syndromes

May be genetic or acquired. Classified by anatomical distribution of liposytrophy:

  • congenital generalised LD: autosomal recessive, generalised absence of adipose tissue, increased appetite (absence of leptin), DM develops in 10-20yrs
  • familial partial LD 1 (FPLD1): loss of limb fat, increased truncal fat, no identified gene to date
  • FPLD2: loss of function mutation identified
  • FPLD3: paucity of limb and gluteal fat, loss of function mutation in PPARg

Clinical features: partial or complete absence of adipose tissue, insulin resistance a feature of most, clinical expression more pronounced in women

Dx is clinically based.

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Diabetes and HIV

Incidence of diabetes in HIV+ men treated with HAART is 4x greater than in HIV- men.

Pathophysiology: high levels of insulin, proinsulin and glucagon, insulin resistance may have an HIV component, protease inhibitors also implicated

Protease inhibitors and NRTIs: associated with increased risk of insulin resistance and diabetes, effects on glucose metabolism varied, indinavir blocks insulin-mediated glucose uptake by blockade of GLUT-4 and also increases hepatic glucose production

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