For decades it is well known in ophthalmology that a large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy. This was demonstrated on type I (insulin dependent) diabetics after insulin injection in study from Oslo (Br Med J (Clin Res Ed). 1985 March 16; 290(6471): 811–815).

I thought this review by Lloyd Paul Aiello, MD, PhD, Jerry Cavallerano, OD, PhD, would be useful to this discussion: http://www.medscape.com/viewarticle/452955

The Diabetes Control and Complications Trial (DCCT) definitively demonstrated that intensive control of blood glucose levels in patients with type 1 diabetes mellitus substantially reduces the risk of onset and progression of diabetic retinopathy.[1,2] In addition, the reduced risks of onset and progression of retinopathy associated with intensive therapy persisted at least 4 years beyond the conclusion of the DCCT, despite near convergence of hemoglobin A1c levels in the intensive-therapy and conventional-therapy groups.[3]

The United Kingdom Prospective Diabetes Study (UKPDS) found similar benefits of intensive blood glucose control for patients with newly diagnosed type 2 diabetes.[4] In the Kumamoto study in Japan of patients with type 2 diabetes who were taking insulin, the benefits of intensive control of blood glucose levels were likewise demonstrated.[5]

The DCCT documented "early worsening" of diabetic retinopathy in the study population.[6] Early worsening of retinopathy occurred in 13.1% of 711 patients assigned to intensive treatment and in 7.6% of 728 patients assigned to conventional treatment. Nevertheless, after 18 months this early worsening in retinopathy reversed, and patients in the intensive-treatment group fared better than those on conventional therapy.

In the DCCT, the long-term benefits of intensive control clearly outweighed the risk of early worsening of retinopathy, and no case of early worsening resulted in serious visual loss. Based on these findings, it is recommended that persons with type 1 or type 2 diabetes initiate intensive therapy as early as possible, and maintain intensive therapy for as long as possible, with the expectation that intensive control of blood glucose levels will reduce the risk of onset and progression of diabetic retinopathy. For patients with elevated hemoglobin A1c levels, careful retinal evaluation, close retinal follow-up, and laser photocoagulation (or anti-VEGF nowadays) as indicated are important components of care as intensive therapy is initiated.

References

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.

2. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol. 1995;113:36-51.

3. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med. 2000;342:381-389.

4. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-853.

5. Shichiri M, Kishikawa H, Ohkubo Y, Wake N. Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients. Diabetes Care. 2000;23(suppl 2):B21-B29.

6. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998;116:874-886.

I am not a physician, but retinopathy associated with intensive insulin therapy is most likely due to issues with episodic hypoglycemia, rather than the insulin action itself. Tightly managing glucose control with insulin is very difficult, especially in an out-patient setting, and frequent bouts of hypoglycemia are fairly common. I would think it is better to error on a slighlty higher fasting glucose rather than set a low target and have frequent nightime or fasting hypoglycemia.

A minority of patients (approx 6%) suffer from worsening retinopathy/retinal haemorrhage following intensification of glycaemic control and I would suggest that the majority should not be disadvantaged because of this concern. It is however important to discuss this with patients. My own experience is following islet and pancreas transplantation where a similar incidence is seen hence my reference above to improved glycaemic control rather than intensification or initiation of insulin therapy. It is believed to be this improvement in glycaemic control that matters. Purely anecdote, but my own practice was to ensure retinal screening whilst wait listed for a transplant and to work closely with ophthalmologists to treat active disease aggressively with a suggestion that this reduced the incidence of complications post-op but we still had a few patients who had real problems. This addresses the question of the role of episodic hypoglycaemia as these patients have improved control without hypoglycaemia but still on occasion get into trouble.

Both excessive insulin and glucose are known to be harmful, so the goal with diabetes should be to have lower levels of both. Insulin resistance is mainly driven by excessive fructose from sugar and HFCS so these dietary elements must be limited.

Ketogenic (low carbohydrate, moderate protein, high fat) diets look promising for the treatment of diabetes because they result in lower insulin and glucose levels:

http://www.ncbi.nlm.nih.gov/pubmed/23680948

I have to confess to being wary of low carb, moderate protein high fat diets. One of the greatest burdens for many people with diabetes is dietary restriction. Furthermore, please excuse my ignorance, but what would the impact of this diet be on macrovascular complications? The high fat component concerns me. I am also interested in the statement that insulin resistance is mainly driven by excessive fructose. What is the evidence for this? I note the publication you cite with interest and look forward to the clinical studies.

Sudden tight blood sugare control deteriorates diabetic retinopathy independant of hypoglicaemic drugs used - insulin or others. Blood sugare drop initiates hemorrhages

I agree! As above, the haemorrhages seen in a minority of patients post successful pancreas transplantation confirm that insulin is not the cause.

Richard:

There is some preliminary evidence that ketogenic diets may improve metabolic markers in diabetes:

http://www.biomedcentral.com/content/pdf/1743-7075-5-36.pdf

http://www.biomedcentral.com/content/pdf/1743-7075-2-34.pdf

http://jn.nutrition.org/content/132/7/1879.full

My friend Richard Johnson has done a lot of work on the role of fructose in insulin resistance:

http://obesity.jou.ufl.edu/resources/fructose-uric-acid.pdf

http://ajcn.nutrition.org/content/86/4/899.full

I am a ophthalmologist. As Daniel suggested, retinopathy associated with intensive insulin therapy may be due to issues with episodic hypoglycemia in some cases. But sudden hypoglycemia cause the VEGF production in retina.

For decades it is well known in ophthalmology that a large and rapid fall in blood glucose concentration may promote transient deterioration of diabetic retinopathy. This was demonstrated on type I (insulin dependent) diabetics after insulin injection in study from Oslo (Br Med J (Clin Res Ed). 1985 March 16; 290(6471): 811–815).

I thought this review by Lloyd Paul Aiello, MD, PhD, Jerry Cavallerano, OD, PhD, would be useful to this discussion: http://www.medscape.com/viewarticle/452955

The Diabetes Control and Complications Trial (DCCT) definitively demonstrated that intensive control of blood glucose levels in patients with type 1 diabetes mellitus substantially reduces the risk of onset and progression of diabetic retinopathy.[1,2] In addition, the reduced risks of onset and progression of retinopathy associated with intensive therapy persisted at least 4 years beyond the conclusion of the DCCT, despite near convergence of hemoglobin A1c levels in the intensive-therapy and conventional-therapy groups.[3]

The United Kingdom Prospective Diabetes Study (UKPDS) found similar benefits of intensive blood glucose control for patients with newly diagnosed type 2 diabetes.[4] In the Kumamoto study in Japan of patients with type 2 diabetes who were taking insulin, the benefits of intensive control of blood glucose levels were likewise demonstrated.[5]

The DCCT documented "early worsening" of diabetic retinopathy in the study population.[6] Early worsening of retinopathy occurred in 13.1% of 711 patients assigned to intensive treatment and in 7.6% of 728 patients assigned to conventional treatment. Nevertheless, after 18 months this early worsening in retinopathy reversed, and patients in the intensive-treatment group fared better than those on conventional therapy.

In the DCCT, the long-term benefits of intensive control clearly outweighed the risk of early worsening of retinopathy, and no case of early worsening resulted in serious visual loss. Based on these findings, it is recommended that persons with type 1 or type 2 diabetes initiate intensive therapy as early as possible, and maintain intensive therapy for as long as possible, with the expectation that intensive control of blood glucose levels will reduce the risk of onset and progression of diabetic retinopathy. For patients with elevated hemoglobin A1c levels, careful retinal evaluation, close retinal follow-up, and laser photocoagulation (or anti-VEGF nowadays) as indicated are important components of care as intensive therapy is initiated.

References

1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977-986.

2. The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial. Arch Ophthalmol. 1995;113:36-51.

3. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med. 2000;342:381-389.

4. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-853.

5. Shichiri M, Kishikawa H, Ohkubo Y, Wake N. Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients. Diabetes Care. 2000;23(suppl 2):B21-B29.

6. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol. 1998;116:874-886.

It is evidence-based that tight glucose control, I mean suddenly drop of sugar, could worsen diabetic retinopathy, that is why is always recommended to decrease sugar gradually to prevent deterioration of diabetic retinopathy.

Marrianne--When you recommend decreasing sugar gradually I suspect that you are referring to glucose. I agree that stable glucose levels are important and extreme highs and lows can be damaging.