management of type 2 diabetes insulin
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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
A Desktop Guide to Type 2 Diabetes Mellitus, European Diabetes Policy Group 1999
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
A Desktop Guide to Type 2 Diabetes Mellitus, European Diabetes Policy Group 1999
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: