Remissione del diabete tipo 2: Terapia Medica

Dr. Monica NannipieriDipartimento di Medicina Clinica e Sperimentale

Università di Pisa

Adapted from De Fronzo RA, Diabetes 2009

IncreasedGlucagonSecretion

NeurotransmitterDysfunction

DecreasedIncretin Effect

IncreasedHGP Decreased

Glucose Uptake

IncreasedGlucoseReabsorption

IncreasedLipolysis

Hyperglycemia

DecreasedInsulin

Secretion

Islet- cell

1. Effective treatment of type 2 diabetes requires multiple drugs used in combination to correct multiple pathophysiological defects

2. Treatment should be based on known pathogenic abnormalities and not simply on reduction of HbA1C3. Therapy must be started early in the natural history of type 2 diabetes to prevent progressive beta-cell failure

Therapeutic implications of the pathogenesis of type 2 diabetes

Therapeutic implications of the pathogenesis of type 2 diabetes

Therapeutic implications of the pathogenesis of type 2 diabetes

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

• Glycemic targets

- HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l])

- Pre-prandial PG <130 mg/dl (7.2 mmol/l)

- Post-prandial PG <180 mg/dl (10.0 mmol/l)

- Individualization is key:

Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0%+) - older, comorbidities,

hypoglycemia prone, etc.

- Avoidance of hypoglycemia

PG = plasma glucose

Diabetes Care 2012, Diabetologia 2012

Therapeutic implications of the pathogenesis of type 2 diabetes

Consider initial

Consider initial

insulin therapy

insulin therapy

when A1c >10-12%

when A1c >10-12%Consider initial

Consider initial

insulin therapy

insulin therapy

when A1c >10-12%

when A1c >10-12%

Begin with these

Begin with these

options if metformin

options if metformin

contraindicated

contraindicatedBegin with these

Begin with these

options if metformin

options if metformin

contraindicated

contraindicated

Consider initial dual

Consider initial dual

combination therapy

combination therapy

when A1c >9%

when A1c >9%Consider initial dual

Consider initial dual

combination therapy

combination therapy

when A1c >9%

when A1c >9%

Diab Care, vol 32 n 11 November 2009

[..] For a chronic illness such as diabetes, it may be more accurate to use the term remission than cure. Current or potential future therapies for type 1 and type 2 diabetes will likely always leave patients at risk for relapse, given underlying pathophysiologic abnormalities and/or genetic predispositionThe authors agreed upon the following definitions, which are the same for type 1 and type 2 diabetes: Remission is defined as achieving glycemia below the diabetic range in the absence of active pharmacologic (anti-hyperglycemic medications, immunosuppressive medications) or surgical (ongoing procedures such as repeated replacement of endoluminal devices) therapy

Buse JB et al. Diab Care 2009

HbA1c < 6.5%Glycemia 100-125 mg/dl

HbA1c < 6.0%Glycemia < 100 mg/dl

Mingrone G NEJM 2012

Bariatric Surgery versus Conventional Medical Therapy for Type 2 Diabetes

6.5

DIABETES REMISSION AFTER WEIGHT LOSS INTERVENTION

Gregg EW JAMA 2012

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

Randomized control trial, 4 years follow-up 4503 pts

Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 2012.

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

Chen A, Diabetes Care 2012

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

118 pts in CSII for 2 wks,53 non remission65 in remission for >1year

Liu J End Jap 2012

68.9%60.6%

49.5%

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy? -cell Function

188 patients

Liu J End Jap 2012

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

Wen XU, Chin Med J 2009

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

84 patients42 patients 42 patients

Weng J, Lancet 2008

Retnakaran R, Zinman B, Diabetes, Obesity and Metabolism, 2012.

Predictors of successful sustained euglycemia

Is it possible to have Remission of Type 2 Diabetes with Medical Therapy?

When?

SUMMARY

The effects of medical treatment on diabetes are related to improvement

or restoration of:

a.insulin sensitivity (life style, weight loss);

.-cell function (hormonal factors and reduction of glucotoxicity and

lipotoxicity).

Rate of success of medical treatment in terms of diabetes remission may

depend on the extent of -cell dysfunction/loss at time of treatment and,

hence, could be lower for:

a.longer diabetes duration;

b.less BMI.