Management of Type 2 Diabetes INSULIN

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Management of Type 2 DiabetesINSULIN
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Pathogenesis of Type 2 Diabetes
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Insulin secretion profiles in Type 2 diabetic
patients and healthy persons
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Insulin secretion in Type 2 diabetic patients

• Amount of insulin released over 24 hours similar
  to control levels
• Irregular pulses of lower amplitude
• Slow increase after meal
• No return to basal levels between meals

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Secondary Failure
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Glycaemic Control Type 2

• United Kingdom Prospective Diabetes Study (UKPDS)
• 3867 patients 20 year follow up
• Endpoints evaluated
• Would intensive pharmacological control of blood
  glucose improve outcome?
• Was outcome affected by treatment choice?

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UKPDS - Glycaemic control
Conventional policy
Intensive policy
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9
10
8
9
Median HbA1c ()
Median FPG (mM)
8
7
7
6
0
0
15
12
9
6
3
0
15
12
9
6
3
0
Time from randomisation (years)
UKPDS Group Lancet 1998352837
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UKPDS - Conventional vs Intensive Therapy

• Over first 10 years from diagnosis
• FPG and HbA1c increased in both groups due to
  deterioration of beta cell function
• But 11 reduction in HbA1c on intensive policy vs
  conventional policy (median 7.0 vs 7.9
  plt0.0001)

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Correlation between HbA1c Plasma Glucose
HbA1c Mean plasma glucose 6 7.5 7 9.
5 8 11.5 9 13.5 10 15.5 11 17.5 12
19.5
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UKPDS key outcome results
Any diabetes- related endpoint
Risk reduction, intensive versus conventional
treatment groups.
Microvascular endpoint
Cataract extraction
Retinopathy (12 years)
Myocardial infarction
Albuminuria (12 years)
0
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Risk reduction ()
p lt 0.05 p lt 0.01
20



30

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UKPDS Conclusions

• Reducing the risk of microvascular complications
  in Type 2 diabetes is a realistic goal !
• Intensive blood glucose control reduces risk of
  complications

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Treatment Type 2 Diabetes
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Type 2 diabetes is a progressive disease

• Progressive loss of beta cell function is
  observed during the natural course of the disease
• Many patients need combination therapy
• 5-10 of the patients treated with oral agents
  will start insulin every year
• At 6 years 50 of patients in the UKPDS were
  receiving insulin to maintain good glycaemic
  control

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Stages to reach and maintain the targets

• Diet and exercise
• Oral hypoglycaemic agents monotherapy
• Oral hypoglycaemic agents combination therapy
• OHA s Nocte Insulin therapy
• OHAs (IS) Insulin Therapy

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Begin an oral agent when

• An adequate trial of life-style intervention/
  education has been given
• either (usually) HbA1c gt 6.5, venous FPG
  gt 6.0 mmol/L (gt110 mg/dl)
• or (occasionally) if the patient is thin and
  there are no other arterial factors HbA1c gt
  7.5,
• venous FPG gt 7.0 mmol/L (gt 125 mg/dl)

A Desktop Guide to Type 2 Diabetes Mellitus,
European Diabetes Policy Group 1999
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OADs 5 classifications
Sulphonylureas (SU)
Insulin Secretagogues
Prandial Glucose Regulators (PGRs)

Biguanides
Insulin Sensitisers
Thiazolidinediones (TZDs)
a-Glucosidase Inhibitors
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Maximum Dose Guide for OADs
4 Refer to MIMS Annual for information on
these and other OADs
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Monotherapy and Combination Therapy

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Guidelines for Starting Insulin
Insulin therapy is indicated if the following
measures fail to achieve glycaemic targets

• Maximum tolerated dose of Oral Hypoglycaemic
  Agents (OHA)
• Failure to reach glycaemic targets (6/12)
• Remediable factors considered (e.g. food and
  exercise plan, intercurrent problems)

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Targets for glycaemic control in Type 2 diabetes

• Fasting/preprandial BG lt 6.0 mmol/L
• Postprandial BG lt 7.7 mmol/L
• HbA1c lt 7.0

Self-monitored blood glucose
A Desktop Guide to Type 2 Diabetes Mellitus,
European Diabetes Policy Group 1999
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Insulin therapy in Type 2 diabetes maxing out
on oral therapy

• Begin insulin therapy when HbA1c gt 8.0 after
  maximum attention to dietary control and oral
  glucose lowering therapy
• Review diet before starting insulin
• Review (or start) self-monitoring of blood
  glucose before starting insulin therapy
• Continue therapy with metformin/insulin
  secretagogues/ PPAR - agonists

A Desktop Guide to Type 2 Diabetes Mellitus,
European Diabetes Policy Group 1999
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Treatment Options

• Bedtime Insulin and Daytime OHA
• Replacement Insulin Therapy twice daily insulin
• Intensive therapy QID (rarely indicated)

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Combination Therapy

• Maintain sulfonylurea and metformin doses
• Add evening Protaphane dose

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How to START insulin therapy
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Bedtime Insulin Daytime Oral Agents
OADs during the day
Protaphane InnoLet at bedtime
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• If more than 30-36 IU of insulin necessary to
  obtain good metabolic control, consider stopping
  insulin secretagogues and continue on same total
  dose of insulin metformin or actos
• Divide the dose into 2 daily injections
• 2/3 before breakfast
• 1/3 at bedtime

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Start insulin twice a day
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Replacement Therapy- Twice Daily Insulin
2/3 Daily dose given in the morning
1/3 Daily dose given in the evening
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Points to Consider

• Education regarding
• Diet and exercise
• Blood glucose monitoring
• Hypoglycaemia
• Improved control may result in
• Weight gain

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Additional tips

• Do not alter insulin doses frequently
• Go slowly
• Adjust every few days based on a pattern
• Diet/ education/ activity critical
• If you get stuck call us at DCAS if CVR gt15 in
  next 5 years

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Summary

• Early and aggressive treatment of Type 2 diabetes
  to improve glycaemic control decreases the risk
  of long-term complications
• Type 2 diabetes is a progressive disease
  progressive loss of beta cell function is
  observed during the natural course of the disease
• Insulin treatment should be initiated when near
  normalization of blood glucose cannot be achieved
  with OHAs

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DIABETES An epidemic!!!
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The role of the GP

• Sheer necessity
• Frequent follow-up
• Better patient familiarity
• Consultant back-up can be supportive and
  occasional specify.
• Complex cases and type I diabetes need to have
  interactive endocrinologist care.

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?
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STENO-2 STUDY
160 patients with T2D and the metabolic syndrome,
including microalbuminuria, randomised to either
conventional therapy at their GPs, or intensive
care at Steno Diabetes Centre.
P. Gaede, P. Verdel, N. Larsen, et al. N Engl J
Med. 2003348383-393
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• Individualised risk assessment
• Ambitious goal setting
• More drugs/higher doses
• Continued patient education/motivation

Drug treatment stepwise and target driven
Hyperglycaemia Metformin - Gliclazide Insulin
per charts Dyslipidaemia Statins
Fibrates Hypertension ACE Inhibitors -
Angiotensin II blockers Diuretics - Calcium
antagonists - Beta-blockers Albuminuria ACE
Inhibitors Other CVD prevention Aspirin
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STENO-2 Follow up at 8 yrs
Intensive
Conventional

• HbA1C () 9.0 7.9
• Systolic BP (mmHg) 146 131
• Diastolic BP (mmHg) 78 73
• Total chol (mM) 5.6 4.1
• LDL chol (mM) 3.3 2.1
• Triglycerides (mM) 3.0 1.7

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Steno-2 Microvascular complications after 8 years
Nephropathy
0.39
Relative Risk
0.42
Retinopathy
Auton Neuropathy
0.37
Periph Neuropathy
1.09
1.0
1.5
2.0
2.5
0
0.5
In favour of intensive
In favour of conventional
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Steno-2 Cardiovascular endpoints after 8 years
65 CVD events in 35 conventional patients
(44) 33 CVD events in 19 intensive patients
(24)
Probability for primary endpoint
0.6
Conventional
0.5
0.4
0.3
Intensive
0.2
0.1
0
0
12
24
36
48
60
72
84
96
Months of follow-up
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Fundamental message

• Diabetes management - aggressive
• Lifestyle is critical in ALL
• Target all CVRF
• Manage Hyperglycaemia
• Screen for and manage complications
• We do not do a good job of reaching targets in
  this condition
• Challenge

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We can do this as a team

• Feasible
• Sustainable
• Affordable
• Effective
• Model of diabetes care for Australia
• Centered around self efficacy and GP based care
  with expert support

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Questions