Is it type 2 diabetes? Gerry Rayman

Type 1 vs Type 2 More dramatic presentation- short history of severe polydipsia & polyuria Younger Weight loss Ketones Strong FH of Type 1 Often no osmotic symptoms Age related More common amongst certain ethnic groups Central obesity & other features of metabolic syndrome FH of Type 2

32 yr old woman presents with 6 months of lethargy and recurrent thrush Random blood glucose 11 mmol/l, BMI 27 FH of type 2 diabetes in both parental GM No ketones type 1 or type 2

Type 1? Type 2? Unsure ? Other ? Not diabetic? What else would you like to know? Type 1 or Type 2

32 yr old woman presents with 6 months of lethargy and recurrent thrush Random blood glucose 11 mmol/l, BMI 27 FH of type 2 diabetes in both parental GM No ketones Type 1 or Type 2

32 yr old woman presents with 6 months of lethargy and recurrent thrush Random blood glucose 11 mmol/l, 76 kg, BMI 27 FH of type 2 diabetes in both parental GM No ketones FBG 8.0 Type 1 or Type 2

Type 1? Type 2? Unsure ? Other ? Not diabetic? If none of above what else would you like to know? Type 1 or Type 2

Criteria for the diagnosis of diabetes 1. HbA1C ≥ %. OR 2. FPG ≥ mmol/l OR 3. 2-h plasma ≥ mmol/l) during an OGTT. OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma ≥ 11.1 mmol/l).

Criteria for the diagnosis of diabetes 1. HbA1C ≥6.5%. OR 2. FPG ≥ mmol/l OR 3. 2-h plasma ≥ mmol/l) during an OGTT. OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma ≥ 11.1 mmol/l).

Criteria for the diagnosis of diabetes 1. HbA1C ≥6.5%. OR 2. FPG ≥ 7.0 mmol/l OR 3. 2-h plasma ≥ mmol/l) during an OGTT. OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma ≥ 11.1 mmol/l).

Criteria for the diagnosis of diabetes 1. HbA1C ≥6.5%. OR 2. FPG ≥ 7.0 mmol/l OR 3. 2-h plasma ≥ 11.1mmol/l) during an OGTT. OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma ≥ 11.1 mmol/l).

Criteria for the diagnosis of diabetes 1. HbA1C ≥6.5%. OR 2. FPG ≥ 7.0 mmol/l OR 3. 2-h plasma ≥ 11.1mmol/l) during an OGTT. OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma ≥ 11.1 mmol/l). *In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing.

Diet and exercise 12 months later HbA1c 7.2% on metformin 500 mg bd Lethargic but pleased at loss of 5 kilos Initial management

18 months since diagnosed Weight reduced another 3 kg (BMI 24) On maximum doses of metformin & gliclazide Feeling ‘crap’ Thrush persists Frequently off work HbA1c 7.4%

Type 1? Type 2? Unsure ? Other ? What else would you like to do ? Type 1 or Type 2

Case 1 Refer her to the Diabetes Centre. 18 months of feeling crap with recurrent thrush, 8 kg weight loss, a BMI now 22 and only adequate control despite max OHA Even though HbA1c satisfactory she must have type 1 diabetes GAD (Glutamic Acid Decarboxylase) antibodies >1000 Within 4 weeks of insulin therapy remarkable improvement in life.

Allen’s ladder Elizabeth Hughes Clung to life for 2 yrs weighed 45 lb at age of 16yr

Case 2 29 yr man- BMI 24 Age 17 yr, episode of ‘slightly’ high glucose when had glandular fever (Romford) FGB FBG FBG HbA1c 7.2%

Type 1? Type 2? Unsure ? Not diabetic? Any additional questions you would like to ask? Type 1 or Type 2

Case 2 FH father diagnosed age 40 only ever diet controlled and paternal GM diet controlled age 97 OGTT 2008 Basal hour 7.3 mmol/L (HbA1c 7.3)

Case 3 27 yr old female- BMI 24 Attending DESMOND training Diagnosed type 2 following OGTT 2012 Basal 7.2 and 2 hour 8.4 mmol/L (HbA1c 6.8%)

Case 3 27 yr old female- BMI 24 Attending DESMOND training Diagnosed type 2 following OGTT 2012 Basal 7.2 and 2 hour 8.4 mmol/L (HbA1c 6.8%) FH mother, maternal aunt and grandmother

What is Maturity-Onset Diabetes of the Young? Maturity-Onset Diabetes of the Young or MODY affects 1-2% of people with diabetes, although it often goes unrecognised. The 3 main features of MODY are: Diabetes that develops before the age of 25 Runs in families from one generation to the next Diabetes may be treated by diet or tablets and does not always need insulin treatment Autosomal Dominant Inheritance. All children of an affected parent with MODY have a 50% chance of inheriting the affected gene and developing MODY themselves.

Why is it important to recognise it? There are different types of MODY for which the treatments are quite different. The progression and risk of complications is different for each type and quite different from type 1 and 2 diabetes. As it runs in families, it is important to advise other family members of their risk of inheriting it. Pregnancy

Case 4 37 yr old who had insulin requiring gestational diabetes in 2005 and 2009 Over 18 months, persistent lethargy, stone weight loss, thrush, nocturia x 3. Presents with ear infection, BMI 28- random glucose 17.2 Started on metformin

Type 1? Type 2? Unsure ? Other ? What would you do ? Type 1 or Type 2

Case 4 3 months later referred- HbA1c 10.4 Started on basal/bolus insulin 4 months later- resolution of thrush, nocturia and lethargy. Most recent HbA1c 5.6% GAD antibodies >2000

Case 5 Mrs A C aged 51 Presents with 18/12 recurrent thrush, thirst, polyuria, nocturia x 3. PMH hypertension, depression, osteoporosis (traumatic wrist fracture) FH- mother type 2 diabetes developed aged 79 Medications- Ramipril, bendroflumethiazide, simvastatin, alendronate BMI 32 and 8 kg gain in the last 2 yrs HbA1c 7.9%, FBG 8.9

Type 1? Type 2? Unsure ? Other ? Type 1 or Type 2

Case 5 Mrs A C aged 51 Presents with 18/12 recurrent thrush, thirst, polyuria, nocturia x 3. PMH hypertension, depression, osteoporosis (traumatic wrist fracture) FH- mother type 2 diabetes developed aged 79 Medications- Ramipril, bendroflumethiazide, simvastatin, alendronate BMI 32 and 8 kg gain in the last 2 yrs HbA1c 7.9%, FBG 8.9

Case 5 Mrs A C aged 51 Presents with 18/12 recurrent thrush, thirst, polyuria, nocturia x 3. PMH hypertension, depression, osteoporosis (traumatic wrist fracture) FH- mother type 2 diabetes developed aged 79 Medications- Ramipril, bendroflumethiazide, simvastatin, alendronate BMI 32 and 8 kg gain in the last 2 yrs HbA1c 7.9%, FBG 8.9

Case 5 Mrs A C aged 51 Presents with 18/12 recurrent thrush, thirst, polyuria, nocturia x 3. PMH hypertension, depression, osteoporosis (traumatic wrist fracture) FH- mother type 2 diabetes developed aged 79 Medications- Ramipril, bendroflumethiazide, simvastatin, alendronate BMI 32 and 8 kg gain in the last 2 yrs HbA1c 7.9%, FBG 8.9 DIAGNOSIS – Cushing’s Syndrome

Etiologic classification of diabetes mellitus I. Type 1 diabetes II. Type 2 diabetes III. Other specific types A.Genetic defects of b-cell function 1.MODY 3 (Chromosome 12, HNF-1a) 2.MODY 1 (Chromosome 20, HNF-4a) 3.MODY 2 (Chromosome 7, glucokinase) 4.HNF-1B (renal cysts-hepatocyte nuclear factor-1ß gene) Other very rare forms of MODY 5. Transient neonatal diabetes (most commonly ZAC/HYAMI imprinting defect on 6q24) 6. Permanent neonatal diabetes (KCNJ11gene encoding Kir6.2 subunit of b-cell KATP channel) 7. Mitochondrial DNA

8. Others B. Genetic defects in insulin action Type A insulin resistance, Leprechaunism, Rabson-Mendenhall syndrome, Lipoatrophic diabetes C. Diseases of the exocrine pancreas 1. Pancreatitis 2. Trauma/pancreatectomy 3. Neoplasia (presenting with DM or existing DM that worsen) 4. Cystic fibrosis 5. Haemochromatosis D. Endocrinopathies 1. Acromegaly 2. Cushing’s syndrome 3. Glucagonoma 4. Pheochromocytoma 5. Hyperthyroidism 6. Somatostatinoma 7. Aldosteronoma 8. Others

E. Drug or chemical induced Vacor, Pentamidine, Nicotinic acid, Glucocorticoids, Thyroid hormone, Diazoxide, b-Adrenergic agonist, Thiazides, Dilantin, g-Interferon, Statins F. Infections 1. Congenital rubella 2. Cytomegalovirus G. Uncommon forms of immune-mediated diabetes 1. “Stiff-man” syndrome 2. Anti-insulin receptor antibodies H. Other genetic syndromes sometimes associated with diabetes 1. Down syndrome 2. Klinefelter syndrome 3. Turner syndrome 4. Wolfram syndrome (DIDMOAD) 5. Friedreich ataxia 6. Huntington chorea 7. Laurence-Moon-Biedl syndrome 8. Myotonic dystrophy 9. Porphyria 10. Prader-Willi syndrome

Case 6 "It started last November. I'd had a bad cold and cough. My GP did a blood test which showed a very high sugar level - that's what revealed the diabetes. "The symptoms were tiredness, and drinking a lot of water. But I do anyway. "There was weight loss but then I was already making an effort to be careful about diet and to get my gym sessions in. "Tiredness is part of the job. It is full on." Initially doctors thought I had Type 2 diabetes but 6 months later it was revealed to be Type 1 diabetes.

Case 6 "It started last November. I'd had a bad cold and cough. My GP did a blood test which showed a very high sugar level - that's what revealed the diabetes. "The symptoms were tiredness, and drinking a lot of water. But I do anyway. "There was weight loss but then I was already making an effort to be careful about diet and to get my gym sessions in. "Tiredness is part of the job. It is full on." Initially doctors thought I had Type 2 diabetes but 6 months later it was revealed to be Type 1 diabetes.

Case 7 Macey aged 48 yr Trying to loose weight since Xmas 2012 May, presented to GP with dramatic weight loss over 2 month & thirst Diagnosed as type 2 diabetes and started on MF Read about Theresa May after discussion with Practice nurse referred HbA1c >14.0% Now asymptomatic and managing well on insulin

The Theresa May Syndrome!

What is the message 95% of patients will have type 2 diabetes but 1/20 will not The 5% are important How do we spot these? Think laterally- the mistake is to think “adults have type 2 and children type 1, so this adult must have type 2” You need to have the Sherlock Homes approach- sniff out what is not quite right

Making the annual foot examination assessment more interesting and effective Using it to assess patient’s knowledge To educate the patient To have them on the right care pathway

Incidents per 1000 prevalent cases by CCG

Type 1 or Type 2 14 yr old caucasian girl presents with moderate thirst, polyuria, nocturia X3-4, listleness Blood glucose 32 mmol/l Ketones + BMI 32 Mother Type 2 diabetes BMI 34

What would be the correct approach? Treat as type 1 diabetes Treat as type 2 diabetes Not sure- start on insulin Not sure- diet and sulphonylurea Not sure- diet and metformin

Type 2 diabetes Very high c-peptide and insulin levels Negative insulin anti-bodies Managed on insulin and metformin Acanthosis Nigricans