Management of Type 2 Diabetes INSULIN

Management of Type Management of Type 2 Diabetes2 Diabetes

INSULININSULIN

Glucose-induced insulin secretion

Tissue response to insulin

Impairedbeta cellfunction

Basal hyper- insulinemia

Post receptor defect

Glucosetransport

Insulin binding

Genetic

Acquired

Obesity

Age

Genetic

Acquired

Obesity

Age

Insulin deficiencyInsulin deficiency

Insulin resistanceInsulin resistance

Insulin deficiencyInsulin deficiency

Insulin resistanceInsulin resistance

HyperglycemiaHyperglycemia

Genetic

Acquired Glucotoxicity Lipotoxicity

Genetic

Acquired Glucotoxicity Lipotoxicity

Hepatic glucose production

Glucose uptake

Pathogenesis of Type 2 DiabetesPathogenesis of Type 2 Diabetes

Insulin secretion profiles in Type 2 diabetic patients and healthy persons

Type 2 diabetes

Healthy

Insu

lin s

ecre

t io

n (

pm

ol/m

in)

100

200

300

400

500

600

700

800

Time6 a.m. 10 a.m. 2 p.m. 6 p.m. 6 a.m.10 p.m. 2 a.m.

Insulin secretion in Type 2 diabetic patientsInsulin 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

Secondary Failure

Glycaemic Control – Type 2Glycaemic 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?

UKPDS - Glycaemic controlUKPDS - Glycaemic control

UKPDS Group Lancet 1998;352:837

Time from randomisation (years)

01512963

11

10

0

8

9

7Med

ian

FP

G (

mM

)

Conventional policyIntensive policy

01512963

6

9

0

8

7

Med

ian

HbA

1c (

%)

UKPDS - Conventional vs Intensive UKPDS - Conventional vs Intensive TherapyTherapy

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% p<0.0001)

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

Correlation between HbA1c & Plasma Correlation between HbA1c & Plasma GlucoseGlucose

UKPDS: key outcome resultsUKPDS: key outcome results

0

10

20

30

Any d

iabe

tes-

rela

ted

endp

oint

Micr

ovas

cula

r

endp

oint

Myo

card

ial

infa

rctio

nCat

arac

t ext

ract

ion

Retin

opat

hy

(12

year

s)Alb

umin

uria

(12

year

s)

Ris

k re

duct

ion

(%)

* p < 0.05 ** p < 0.01

*

** *

*

**

Risk reduction, intensive versus conventional treatment groups.

UKPDS ConclusionsUKPDS Conclusions

Reducing the risk of microvascular complications in Type 2 diabetes is a realistic goal !

Intensive blood glucose control reduces risk of complications

Treatment Type 2 DiabetesTreatment Type 2 Diabetes

Type 2 diabetes is a progressive diseaseType 2 diabetes is a progressive diseaseProgressive 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

Stages to reach and maintain the targetsStages 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

Begin an oral agent when:Begin an oral agent when:

An adequate trial of life-style intervention/ education has been given:

either (usually): HbA1c > 6.5%, venous FPG > 6.0 mmol/L (>110 mg/dl)

or (occasionally) if the patient is thin and there are no other arterial factors: HbA1c > 7.5%,

venous FPG > 7.0 mmol/L (> 125 mg/dl)

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

OADs – 5 classifications OADs – 5 classifications

Sulphonylureas (SU)

Biguanides

Thiazolidinediones (TZDs)

α-Glucosidase Inhibitors

Prandial Glucose Regulators (PGRs)

Insulin Secretagogues

Insulin Sensitisers

Maximum Dose Guide for OAD’sMaximum Dose Guide for OAD’s

4 – Refer to MIMS Annual for information on these and other OAD’s

Monotherapy and Combination TherapyMonotherapy and Combination Therapy

Diet and exercise

Oral agents

Insulin

Bet

a-ce

ll fu

nct

ion

Guidelines for Starting InsulinGuidelines for Starting Insulin

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)

Insulin therapy is indicated if the following measures fail to achieve glycaemic targets:

Targets for glycaemic control Targets for glycaemic control in Type 2 diabetesin Type 2 diabetes

Fasting/preprandial BG* < 6.0 mmol/L

Postprandial BG* < 7.7 mmol/L

HbA1c < 7.0 %

* Self-monitored blood glucose


Insulin therapy in Type 2 diabetes Insulin therapy in Type 2 diabetes “maxing out” on oral therapy“maxing out” on oral therapy

Begin insulin therapy when HbA1c > 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


Treatment OptionsTreatment Options

Bedtime Insulin and Daytime OHA

Replacement Insulin Therapy – twice daily insulin

Intensive therapy QID (rarely indicated)

Combination TherapyCombination Therapy

Maintain sulfonylurea and metformin doses

Add evening Protaphane dose

How to START insulin therapyHow to START insulin therapy

Bedtime Insulin & Daytime Oral AgentsBedtime Insulin & Daytime Oral Agents

OAD’sduring the day

Protaphane® InnoLet ® at bedtime

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

Start insulin twice a dayStart insulin twice a day

Replacement Therapy- Replacement Therapy- Twice Daily InsulinTwice Daily Insulin

2/3 Daily dose given in the morning

1/3 Daily dose given in the evening

Points to ConsiderPoints to ConsiderEducation regarding:

Diet and exercise

Blood glucose monitoring

Hypoglycaemia

Improved control may result in:

Weight gain

Additional tipsAdditional 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 >15% in next 5 years

SummarySummary

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

DIABETES: An epidemic!!!

The role of the GPThe 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.

??

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.

Conventional group at GPs

Microvascular Macrovascular

4 Yrs 8 Yrs

Endpoint Examinations

Intensive group at Steno Diabetes Centre80

80

n=160

P. Gaede, P. Verdel, N. Larsen, et al. N Engl J Med. 2003;348:383-393

STENO-2 STUDY

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

• Individualised risk assessment

• Ambitious goal setting

• More drugs/higher doses

• Continued patient education/motivation

STENO-2: Follow up at 8 yrs

• 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

IntensiveConventional

Steno-2: Microvascular complications after 8 years

In favour of intensive In favour of conventional

0 0.5 1.0 1.5 2.0 2.5

Nephropathy

Retinopathy

Auton Neuropathy

Periph Neuropathy

Relative Risk

1.09

0.37

0.42

0.39

Months of follow-up

Probability for primary endpoint

Conventional

Intensive

65 CVD events in 35 ‘conventional’ patients (44%)33 CVD events in 19 ‘intensive’ patients (24%)

Steno-2: Cardiovascular endpoints after 8 years

0

0.1

0.2

0.3

0.4

0.5

0.6

0 12 24 36 48 60 72 84 96

Diabetes management - aggressiveLifestyle is critical in ALLTarget all CVRFManage HyperglycaemiaScreen for and manage complications

We do not do a good job of reaching targets in this condition

Challenge

Fundamental message

We can do this as a teamWe can do this as a teamFeasible

Sustainable

Affordable

Effective

Model of diabetes care for Australia

Centered around self efficacy and GP based care with expert support

Questions:Questions:

Documents

Management of Type 2 Diabetes INSULIN