thrshold where prevalence of moderate diabetic retinopathy begins to increase exponentially

diagnosis

• HbA1c = recommended diagnostic test

  • ≥ 50 with symptoms: DM

  • ≥ 50 with no symptoms: DM but second test

  • 41-49 (6.1-6.9) intermediate hyperglycaemia

    • lifestyle

    • CVD risk

    • follow guidelines

  • ≤ 40 - DM unlikely

• fasting remains useful where HbA1c cannot be used

  • fast for at least 8hrs; pref 12

    • symptomatic

      • ≥ 7.0 (x1 if clear; x2 if borderline)

    • asymptomatic

      • ≥ 7.0 strongly suggests but need another to confirm

        • within 2/52

  • serum glucose levels risen too quickly

    • all children/adolescent suspected of T1DM

    • short duration of symptoms

    • at high risk of DM who are acutely unwell

      • value \< 50 odnes’t exclude

      • where as ≥50 confirms

    • people taking medicines that cause rapid gluose rise for ≤ 2mo

      • corticosteroids

      • antipsychotics

    • acute pancreatic damage - who have had pancreatic surgery

  • condition affect accuracy of HbA1c

    • increased

      • iron deficinency

      • vit b12 impairment

      • renal impairment

      • etoh

      • splenectomy

      • Vit C or E deficiency

      • CKD

      • Aspirin (large doses)

      • chronic opiate use

      • hydroxyurea

    • Decreased

      • iron/vitb12/folate supplementation

      • EPO

      • reticulocytosis

      • chronic liver disease

      • blood loss

      • splenoomegaly

      • RA

      • haemoglobinopathies

      • recent blood transfusion

    • variable

      • haemoglobinopathies

      • sickle cell

      • iron deficinecy anaemia

• pregnant women = continue to use oral glucose tolerance test for GDM with abnormal polycose screen

  • or who have been pregnant in last 2mo

• fructosamine = glycated protein that indicates glycation levels over preceding 14-21d

• testing at any age considered beneficial

Screening

• aymptomatic men >45; women >55yo

• Maori, pacific and indo asian -10yrs earlier

• 3-5 yrs based on risk

• ten years earlier if;

  • fhx of early onset T2DM

  • history gestational dm

  • known ischaemic heart disease, cerebrovascular disease, PVD

  • central obesity or BMI >30 (>27 indo-asian)

  • long term steroid or antipsychotic trematnet

  • intermediate hyperglycaemia on previous assessment

  • adverse lipid profile

  • high BP

  • PCOS

  • current smoker (or quit 12 months)

management

good control known to delay onset of microvascular complications:

• renal failure

• retinopathy

• neuropathy

also benefit for macrovascular if achieved early and maintained

 Target = 50-55

• existing complications;

  • foot, eye, kidney, cvd

    • high risk category

  Managed intensively

Determining level of risk for DM complications

• Low risk

  • HbA1c 50-55

  • BP \<130/80

  • ACR \<2.5M, \<3.5F

  • eGFR ≥60

  • Lipis: TAG \<1.7, total cholesterol \<4.0

  • non smoker

  • attends at least 6monthly review;

    • HbA1c

    • BP

  • annual review:

    • lipids

    • ACR

    • eGFR

    • foot check

  • 2 yearly screening

• Moderate/high (high 3, moderate 2)

  • HbA1c >55

    • risk increases incrementally with increase hba1c

  • BP ≥ 130/80

  • ACR ≥ 2.5 or ≥ 3.5

  • eGFR \<60

  • Lipids;

    • TAG >1.7

    • total cholesterol ≥4

  • Current smoker

  • Ethincity

  • moderate reinopathy (R3, mild maculopathy (M3)

  • more than 1 year since DM last reviewed or poor adherence/attendence

Goals;

• lifestyle advice

  • dietary

  • exercise

  • ABC smoking cessation

• Medication adjustment/intensification

  • improve hylcaemic control - HbA1c 50-55 as individually agreed

  • control BP - \<130/80

    • \<120 = greater frequency of serious adverese effects

      • ACCORD 2010

  • lipid control - TAG \<1.7, total \<4Th

• Ongoing clinical reveiw

  • monitor BP, HbA1c, eGFR 3 monthly

  • ACR 6 monthly

  • Annually

    • weight

    • peripehral neurovascular status

    • cardiovascualr status

    • feet 3mo if complications

  • 2 yearly

    • retinopathy

Lifestyle

• Diet

  • Glycaemic load vs. glycaemic index

    • (carbohydrate x GI)/100

    • Glycaemic index = rate at whcih glucose released into blood stream

    • low: carrots, apples, watermelon, peanuts, kidney beans, chick peas, lentil, spop corn

    • medium: banana, new potato, kumara, jioce

    • high: pasta, cous cous whiete rice

  • fibre

    • only soluable (fruit, vege, legumes, oats) affect glycaemic control

    • increase viscosity and stomach/bowel take longer to empty

    • 25g/d W, 30g/d adult men

  • carbohydrate counting

    • type 1

    • match insulin dose to intake

    • 15g carbohydrate (one slice bread…)

  • diabetic/low sugar foods

    • not necessary

    • more i mprotant to understand label

    • may still be high in kJ and fat

    • “no added sugar” doens’t mean no sugar

    • sugar free may still affect blood glucose

    • fructoes often used

    • lower GI

      • requires less insulin than sucrose

    • fructose may affect TAG and LDL

      • soft drinks, canned fruits,

      • linked with complications of insulin resistance

    • honey == table sugar

• Exercise

  • walking :

    • increase weight loss

    • improve glycaemic control

    • reduce cardiovascular mortality

    • NNT to prevent 1 death with 2 hrs/week wlaking

      • 61

    • compared to NNT metformin = 141

• Self monitoring

  • benefits

    • assisting patients and health practitionsers in ajustment of insulin or other medication

    • encouraging self-empowerment

    • promoting better self-management behaviours

  • negatives

    • may fail to improve diabetes

  • recommended:

    • insulin - YES

    • metformin and other oral: NOT but…

      • at increase risk of hypoglycaemia

      • experiencing acute illness

      • undergoing signiicant changes in pharmacotherpay or fasting

      • unstable or poor glycaemic control

        • HbA1c >64

      • pregnant/planning pregnancy

Metformin

• expected HbA1c reduction: 12-22

• first line for all people

• decreases glucose formation in liver and increase peripheral utilisation of glucose

• particularly effective if overwieght

• may confer cardiovascualr protection beyond glucose lowering

• start low dose to avoid initial GI upset:

  • 500mg od or 250mg od

  • total daily dose shouln’t exceed 2g

• adverse effects

  • diarrhoea - usually transient

  • taste distrubance

  • (decrease vit B12 abdorption)

  • rarely lactic acidosis

    • feature of AKI and acute cardiac / respiratoyr failure

    • in association with CKD

    • if illness -> dehydration: temporarily cease taking metformin

• reduced in patients with eGFR 30-60 (max 1g)

• not begun with significant renal impairment (efGR \<30)

sulfonylurea

• expected HbA1c reduction: 15-20

• add if haven’t reached agreed HbA1c target after 3 months

• increase insulin secretion if patient has functional pancreatic beta cells

  • canc ause hypoglycaemia and weight gain

    • avoid in severe hepatic and renal impairment

• contraindicated in patients with ketoacidosis

• avoided with acute prophyria

• shorter acting:

  • glipizide

    • 2.5-5mg daily with or shortly before breakfast or lunch

    • adjust dose according to response by 2.5-5mg daily at weekly intervals

    • usual maintenece = 2.5-30

    • maximum 40mg daily

    • no more than 15mg in single dose

  • gliclazide

    • 40mg with breakfast

    • up to 160mg single dose

    • maximum 320mg daily

• longer acting:

  • glibenclamide

    • 2.5-5mg daily

    • adjust according to response by 2.5mg daily every 1-2wks

    • maximum 10mg as single dose

    • maximum 15mg daily

    • not recommended older adult

Insulin

• eventually required

• early intiiation can be appropriate

  • beta cell function declines linearly and after 10 years 50% people will require insulin

• shoudn’t be delayed in patients with poor glycaemic control

• result in development of long-term complciations

• discuss fears/personal failing

  • insulin = most effective glucose lowering medicine

  • half of patients with T2DM reported to eventually require insulin to achieve good glycaemic control

• women with T2DM who become pregnant almost always require initiation of insulin

• any person with T2DM where HbA1c not close to previously agreed target or symptoms of hyperglycaemia despinte

  • approriate focus on diet, phsycial exercies, behavioural strategies and other lifestyle interventions

  • appropriate compliance with and odse optimisation of oral hypoglycaemic medicines

• general rule:

  • >65mmol/mol

  • consideration

    • age

    • presence of symptoms

    • long term risk of complications

    • ability to manage insulin treatment

analogues of insulin:

• isophane

  • first line for T2DM

  • intermediate acting

  • maximal effect 4-12hrs

  • Protaphane

  • Humulin NPH

  • once daily:

    • start at 8-10U before meal

    • titrate:

      • BSL >8 and never \<4:

        • increase 4-6U

      • BSL 6-8 and never \<4

        • increase 2-4U

      • once >20 and 3 fasting over target and blood glucose never \<4

        • increase 10-20%

    • at night if pre=breakfast high

      • alert for symptoms of nocturnal hypoglycaemia with doses >20U

    • before breakfast if daytime hyperglycaemia

  • metformin and sulphonylurea should continue

  • if bd dosing:

    • if high blood glucose during day and night or HbA1c >75

    • start with 6-10U bd before meals

    • sulphonyluea should cease

    • titrate:

      • Prebreakfast:

        • >8 and never \<4

          • increase night dose by 4-5

        • 6-8 and never \<4

          • increase night dose by 2-4

      • Preevening

        • generally >8 and never \<4

          • increase pre-breakfast 4-5

        • 7-8 and never \<4

      • once >20u change by 10-20% of daily dose

• Basal insulin analgoues

  • glargine

    • given morning or night where hypoglycaemia is a concern

    • titrated to normalise pre-breakfast glucose levesl

• Premixed insulin

  • fixed ratio of hsort and intermediate

  • given 1 or 2 /day

  • already taking insulin has conssitently hgih blood glucose follwoing meals and where HbA1c targets not being met

  • not intiiated

• seek advice

  • child / adolescent

  • very lean or has lost weight rapidly

    • glutamic acid decarboxylast autoantibodies: indicate T1DM

  • repeated hypoglycaemia

  • vocational driver

  • HbA1c remain above target following insulin initiation and titration

• twice weekly phone-calls recommended with face-face as required to begin with

• one month after initiation

• medication not substitute for healthy lifestyle, smoking,….

• Self monitoring of blood glucose

  • should be performed for approximately one week prior to deciding which insulin regime a patient would benefit from the most

  • before each meal and ideally 2hrs after evening meal and breakfast

  • strips

    • 4 tests/day for 3mo

• needles can be used up to four times

• ensure patient knows:

  • name of insulin they have been prescribed

  • correct dose

  • whether insulin is short, intermediate, long-acting or premixed

  • what cartridge/vial size they need

  • how to correctly match their insulin with required delivery device

• minimize prescription error:

  • use brand name

  • infomr patient details

  • ensure any changes explained and clearly understood

• storage

  • door of fridge

  • stored @ room temperature for up to 28d

  • pen (3mL), syringe (10mL)

  • needle 5-8mm and fine (31g)

Acarbose

• alpha-Glucosidase inhibitor

• expected HbA1c reduction: 6-11

• safe and mildly effective

• reduces amount of glucose absorbed in small intestine

  • blocking alpha-glucosidase enzyme

    • N) breaks down complex carbohydrates into glucose

• Most effective for relieving post prandial hyperglycaemia

  • significant contributor to cardiovascualr disease and the microvascular complications of T2DM

• little effect on fasting levels

• doesn’t increase risk of hypoglycaemia

• when used in combination - enhances hypoglycaemic effect

• start 50mg tds chewed and swallowed with water immediately before eating or with first mouthful

• increase 100mg tds after 4-8wks

• maximum - 200mg tds

• adverse effects

  • flatulence in 3/4

  • soft stool and diarrhoea

  • hepatitis reported

• CI

  • pregnancy

  • hepatic/renal impairment (CKD4)

  • IBD

  • previous abdominal surgery

  • GI disorder with malabsorption

Glitazones (pioglitazone)

• classified as insulin sensitisers

  • increase body’s ability to transport glucose across cell membranes

• don’t cause hypoglyceamia

• associated with:

  • heart failure

    • increase fluid retention

  • bladder cancer

  • increase risk of bone fractures

• Pioglitasone only prep available in NZ

  • special authority

  • already taking max doses of metformin or sulfonylurea or where one or both CI or not toleraited or insulin not achieved glycaemic control

• started if:

  • second line metformin if hba1c >50 or > target and person at significant risk of hypoglycameia or its consequences

  • second line to firstline sulfonylurea if hba1c >50 and patient doens’t tolerate/CI metformin

  • 3rd line if hba1c >59 and insulin neither appropriate or unacceptable

  • combination with insulin if taking high dose insulin and not responded

• initiate

  • 15-50mg od

  • concurrent use increase risk of hypoglycaemia

• only continue if hba1c reduced 5mmol/mol

• associated with weight gain

GLP-1 (glucagon-like peptide 1) agonists

• mimic endogenous incretins

  • peptides with short half-lives secreted from gut following a meal

• enhances endogenous secretion of insulin following eating

• inhibits glucagon secretion

• suppress appetite and food intake

• associated with weight loss in overweight or obese people with or without T2DM

• increase likelihood of pancreatitis x2

• Exenatide (subcut)

  • approved but not subsideised

  • third line

    • bmi ≥ 35

    • or bmi \<35 and insulin inappropriate

Surgical intervention

• effective

• BMI >35

  • when lifestyle and mediicnes ineffective

• NNT diabetes remission @ 2yr follow-up 1.3 (gastric bypass) 1.0 (biliopancreatic diversion)

• how long can maintain this level of glycameic control?????

Complications

diabetic peripheral neuropathy

• see page: neurology

• risk factors;

  • PVD

    • smoking

    • htn

    • hypercholesterolaemia

  • peripheral neuropahty

  • previosu amputaiton

  • previous ulceration

  • presence of callus

  • joint deformity

  • visual/mobility problems

Hypertension

• targe \<130/80

  • \<120= increased adverse events

  • reduce salt by 1 teaspoon/day = 5g = 5mmHg drop in sBP

Renal disease

• Microalbuminuria (ACR >2.5M or >3.5F) earilest sign of diabetic kidney disease

• ACEi/ARB recommended for patients with T2DM and microalbuminauria regardless of whether HTN present

• DM and ACR > 30 on 2 occasions = 5yr CVRA >20%

Diabetic retinopathy

• one of leading causes of blindness and vision impairment

• 30% with DM some degree of retinopathy

  • 10% sight threatening

• longer duration DM -> greater prevalence

• asymptomatic until @ advanced stage

• referral for regualr retinal screening at least every 2 yrs

• screening

  • Type 1:

    • 1st = 5 yrs after diagnosis or after puberty

    • 2 yearly

  • Type 2 DM

    • soon as possible

    • 2 yearly

  • Pregnancy + DM

    • first trimester

    • 2 yearly

• Management

  • duration = most signifiant risk factor

    • poor glycaemic control also major contributor

    • htn

    • nephropathy

  • maintain good glycaemic control

  • manage htn

  • advise re healthy lifestyle

  • blood lipidd

• non proliferative retinopathy

  • microaneurysms

  • haemorrhages

    • dot and blot (deeper) - more common in dm

    • flame = htn

  • hard exudates - leake of srum proteins

  • cotton wool spots - right angles to direction of nerve fibre

  • macular oedema

  • venous loops and beading

• proliferative

  • restricted blood supply -> VGEF -> neovascularisation

  • fragile and easily broken

  • fibrous tissue formed

    • traction = retinal oedema, tears and detachment

Hypoglycaemia

• when bsl \<4

• most common causes:

  • lack of food

  • increase physical activity

  • administration of insulin or less commonly sulphonylurea

  • consumptoin of etoh without food

• symptoms;

  • hunger

  • blurred vision

  • headache

  • light headedness

  • loss of concentration, confusion, irritability

  • sweating, tingling around mouth and lips, trembling, weaknes,s possible loss of conciousness

• management:

  • check blood glucose

  • 10-15g glucose

    • 6 jelly beans, 2-3 glucose tables

    • small glass soft drink (sugar)

  • 5-10min repeat blood glucose

  • should continue until over 4.0

    • eat small meal / snack

  • report episodes of hypoglycaemia

  -

referral

• previous cardiac event/stroke/tia

• eGFR \<45 and / or ACR >30

• severe retinopathy or moderate maculopathy in either eye

• previous amputation/ulceration

• peripehral arterial disease/previous leg vascular disease

follow - up

• at least annually

• should involve

  • HbA1c

  • blood pressure

  • lipid levels

  • assessment of DM related complications

    • CVD

    • kidney disease

    • foot checks

    • retinal complications

  • eucation

Poor glycaemic control HbA1c >64mmol/mol

• relatively common

• numerous reasons

• may be appropriate

• individual approach

  • target-based approach may be harmful

    • older patients with high cardiovascular risk

• Patients beliefs

  • Disease identity

  • cause of type 2 DM

    • belief that just inherited from parents

  • Timeline

    • what is course and how long will it last

  • consequences of type 2 dm

    • belief that introducing insulin means you are going to die soon

  • Cure/control

    • how well the patient will be able to recover from and control their dm

• strength of patient’s belief in ability to influence own health = predictor for adherence to phsyical activity and life satisfaction

• medications influenced by:

  • fear

  • fatalistic acceptance of disease

  • family/whanau’s negative experience with treatment

• What matters to the patient:

  • how important quality of life

  • how motivated to prevent diabetes-related complications

  • patients attitude towards insulin and self-injection

  • is patient concerned about hypoglycaemia

Intermediate hyperglycaemia

• don’t need confirmatory testing if patient is well

• 5-10% progress to DM/year - 70% total

  • RR 6

    • compared to normoglycaemia

  • risk increased

    • age

    • weight/bmi

    • physical activity

    • diet

    • ethnicity - Maori, pacific , south asia

    • smoking

    • fhx diabetes

    • increase blood pressure

    • increase lipid

    • PCOS

• viewed as continuous scale

• many vasuclar complications begin before hba1c reaches diabetic levels

  • nephropathy

  • CKD

  • neuropathy

  • retinopathy

  • cardiovascular disease

  • overall mortality

management

• reduce progression to DM - 30-60% decrease

  • lifestyle changes

    • NNT 6.9

  • initian of metformin wehre appropriate

    • NNT 13.9

    • >60

    • lower body mass index

• agree on target HbA1c

  • \<40

  • repeat test 6/12 - 12/12

• lifestyle

  • everyone

  • 150min moderate exercise

  • gradually lose weight

  • increase consumptino of whole grains, vegetables and other foods high in dietary fibre

  • reduce total amount of fat

  • eat less saturated fat

  • key componenets of effective lifestyle programme

    • meet 8 times over 9-19mo

    • at least 16hrs educational time - group or 1:1

    • follow-up sessions regularly

    • behavioural change techniques used in conjunction with diet and exercise advice

• Add metformin if lifestyle not benefit in 6/12

  • 500mg od