Diabetes

Exercise: Key fact normal people REDUCE insulin secreion during exercise, diabetics on Rx have to do artificially. (Ref)

Summary

Advise	DEWS Diet, Exercise, Weight, Smoking, Feet
Examine	BP (<140/80, <135/75 if Alb+), Feet, Retinal (Yearly)
Labs	HbA1c, Lipids, TFT (Assoc.), UE (Metformin & SU), LFT (SU), Urine Alb (+ && I => ACE even if norm BP)
Drugs	Aspirin, Statin, ACE, ?Vitamins

Drugs

SU

Glibenclamide / Glyburide	Diatab (KFSH)	2nd gen, t1/2 12h	5mg od with breakfast, max 15mg
Glimepiride	Amaryl	3rd gen	1mg steps, max 4mg, exceptional 6mg – shortly before or with first main meal
Gliclazide	Diamicron, Diamicron MR	2nd gen	start 40-80 mg@breakfast, max 160mg as single dose. Daily max 320 but as 160mg bd Dose for MR 30mg daily, max 120mg. Equivalent to 80 mg Diamicron. Adjust dose every 2 weeks
Glipizide	Sucrazide, Minidiab	2nd gen	2.5-5mg od with bfast/lunch. Max 20mg. Max single dose 15mg
Gliquidone	Gliquidone	2nd gen	Initial Dose 15mg bfast. Max dose 180 mg. Max single dose 60mg. Inc doses best to give as tds
Tolbutamide	Tolbutamide	1st gen	Short acting, can use in renal impairment as mainly hepatic elimination.

Hypos rare, indicate overdosage

Evidence

DM II

• BP
  • 2004 BHT Start Rx at >140/90. Targets: No nephropathy (audit 140/80) (optimal 130/80) Nephropathy (<130/80 or <125/75 if >1g/24h)
  • 1998 UKPDS <135/85 reduced morltality by 33%

• HbA1c
  • 1998 UKPDS <7%

• ACE
  • 2004 BHT Type I peristent micro Alb benefit from ACE irrespective of BP

• ARB
  • 2004 BHT If can’t tolerate ACE can take ARB, some evidence that effective

• Intensive SU / Insulin
  • 1998 UKPDS Reduced microvascular complication (eye 25%, early renal 33%). NOT macrovascular in Type II

• Metformin
  • 2007 Prodigy
  • 2007 Review Metformin as good as newer agents from side effect profile
  • 1998 UKPDS Less hypos, reduced complications.

• Aspirin
  • 2004 BHS

• ACE
  • 2001 IRMA II Irbesartan in Hypertension and Microalbiminuria and Type II
  • 2001 IDNT Irbesartan diabetic Nephropathy Trial
  • 2000 HOPE 5yr, >55y, PMH(CVD/DM), Ramipril 10mg v placebo, dec. CVA (32%), MI (20%), death (26%). Dec in deaths could not be explained by hypotensive effect alone.

• Diet
  • 2007 Cochrane Review, no trials looking at diet alone – hence difficult to say what the effect of the various diet regimens are.
  • 2007 Prodigy 60:20:20 % carbohydrate, fat and protein as sources of energy improve diabetic control

• Exercise in Rx
  • 2007 Cochrane Improves glycaemic control whatever the diet
  • 2007 Prodigy 30 minutes 5 times a day – brisk walking

• Meglitinides
  • 2007 Cochrane Reduce HbA1c by about 2%, useful alt. to Metformin. No evidence on long term complications and mortality. Weight gain 3Kg, less GI side effects cf. Metformin

• Long acting insulin
  • 2007 Cochrane Review of insulins versus Isophane, NPH. No reduction in mortality and morbidity. Long acting insulins gave lower hypos. Caution in use advised

• Rosiglitazone
  • 2007 Cochrane Doubles risk of peripheral oedema. CVD risk increased. Increased fractures in women (applies to both Rosi and Pio).
  • 2007 NEJM Meta analysis NNH for MI 375, Odds Ration for cardiovascular death 1.64

Statins
* 2002 PROSPER Pravastatin to elderly 75-82y with pre-existing vascular disease, baseline chol 5.4, red 15% MI. Elderly useful, but note 15% v 33% benefit
* 1996 WOSCOPS 45-64y men, no 6595, DBRCT, Scotland, 40mg pravastatin v placebo, 5yr FU, 31% reduction 1st MI if high cholesterol
* 1997 HPS 40-80y, well but at risk given simvastatin 40mg and antioxidants: 1/3 dec in MI and CVA in DM, PMH(CVA/MI), elderly. Also benefit if cholesterol normal
* 1996 CARE LDL 3-4.5 Rx with Pravastatin 40mg od, RRR 25% MI, 32% of CABG, 31% red in CVA. Benefit women > men. Statins work in secondary prevention even if cholesterol not raised.
* 1994 4S Trial Chol >5.5 & PMH of MI given 40mg simvastatin v placebo: decreases in mortality (30%), CHD Mortality (42%), non fatal MI (37%). Benefits were cumulative over time.

• TFT
  • 2000 Clinical diabetes 30% of Type I females have Thyroid disease. Prev 10% cf non-DM pop. Hyperthyroid => worse Glycaemic control. Poor Dm ctl impairs T4 to 3 conversion. If anti-TPO (Thd Peroxidase) Abs screen yearly for thyroid. 1.6microg/Kg usual full replacement, regular screening required.
  • www.cks.library.nhs.uk/diabetes_glycaemic_control/view_whole_guidance
  • www.medsafe.govt.nz/Profs/adverse/Minutes129.htm

UKPDS
5000 Type II DM
Reduced death (32%), macro (34%) and micro (37%) complications.
Atenolol = captopril = used in study

BHT British Hypertensive Society Guidelines
2004
Very difficult to achieve <130/80 in most clinical trials

DREAM
Diabetes Reduction Approaches with Medications Study (DREAM)

NAVIGATOR
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research