Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes

Kramer, Caroline; Zinman, Bernard; Choi, Haysook; Retnakaran, Ravi

doi:10.1210/jc.2015-1947

Cited by 16 publications

(19 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that pancreatic alpha-cell dysfunction brings out post-prandial paradoxical hyperglucagonaemia which elevates blood glucose levels and thereby contributes to the metabolic dysfunction found in diabetic state [19][20][21][22][23] . We recently reported that diabetic rats expressed GLP-1 receptor in alpha-cells and that GLP-1 analogue stimulated glucagon secretion from alpha-cells but such glucagon secretion was inhibited by simultaneously secreted insulin from beta-cells in paracrine fashion 47 .…”

Section: Discussionmentioning

confidence: 99%

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Nakashima

Okamura

Sanefuji

et al. 2020

Sci Rep

View full text Add to dashboard Cite

the aim is to devise a new short-term intensive insulin therapy (n-Siit) based on the concept of "treat to target" to avoid hypoglycaemia and was applied it to various diabetic state. We determined dosage of 1 basal and 3 bolus "treat" insulin based on "target" blood glucose level and changed each insulin dose by small units (2 units) every day for 2 weeks. We evaluated the effects of N-SIIT in 74 subjects with type 2 diabetes (male 45, female 29, 64.9 ± 16.6 years old, HbA1c 10.4 ± 2.6%). Glargine U300 ("treat") and morning blood glucose level ("target") was significantly correlated with increasing insulin dose and decreasing blood glucose level in day 1-7, indicating that insulin amount was determined by target blood glucose level and lowered next target blood glucose level. Remission rates were 67.3% (Hypoglycaemia rate 5.6 %) in N-SIIT and 47.3% (Hypoglycaemia rate 38.1%) in conventional SIIT. Required amount of insulin would be automatically determined, depending on each patient pathophysiology and life style. This method is pretty simple, flexible and cheap, and provides information about the dynamic pathophysiological alteration of insulin resistance and glucotoxicity from the profile of blood glucose levels and insulin shot.Type 2 diabetes mellitus (T2DM) is a progressive disease which gradually reduces pancreatic beta-cell function such as insulin secretory capacity and increases insulin resistance in various insulin target tissues 1,2 . Recently, short-term intensive insulin therapy (SIIT) is recommended in the treatment of newly diagnosed T2DM to eliminate glucotoxicity, to reduce beta-cell overload (beta-cell rest effect), to support residual beta-cells and to enhance insulin sensitivity 3-18 .In addition, pancreatic alpha-cell dysfunction may contribute to the metabolic dysfunction found in diabetic state, because post-prandial paradoxical hyperglucagonaemia leads to the elevation of blood glucose levels 19,20 . SIIT may also improve alpha-cell physiology 21-23 . Indeed, it is possible that stepwise addition of insulin leads to the reduction of hyperglucagonaemia.The evidence of this treatment has been presented to prove benefits in the treatment of T2DM. However, in most SIIT studies, after SIIT they did not use any anti-diabetic agents and evaluated the duration of glycaemic remission [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] . As the results, glycaemic remission was temporary, especially when beta-cell function was markedly deteriorated after SIIT. Retnakaran et al. regarded SIIT as an induction therapy and sequential treatment with anti-diabetic agents as a maintenance therapy 24 . Several kinds of anti-diabetic agents such as metformin or GLP-1 receptor activator had been used for a maintenance therapy, but sometimes re-induction of insulin therapy was necessary [24][25][26][27] . We used conventional SIIT for the elimination of glucotoxicity in clinical practice and thought that SIIT was useful not only in newly diagnosed T2DM but also under many kinds of diabetes conditions to ...

show abstract

Section: Discussionmentioning

confidence: 99%

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Nakashima

Okamura

Sanefuji

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…There is a wide range of evidence currently available supporting the use of STII therapy in newly diagnosed T2DM. For example, STII can quickly normalize glycemic control, improve β‐cell function, restore first‐phase insulin secretion, and even reduce glucagonemia in newly diagnosed T2DM, suggesting that it may provide unique capacity for modification of the natural process of diabetes …”

Section: List Of Pros and Cons Of Short‐term Intensive Insulin Theramentioning

confidence: 99%

“…Evidence from clinical studies Achieve and sustain prolonged remissions after STII therapy β-Cell function improved, and insulin resistance decreased after STII therapy Post-challenge hyperglucagonemia reduced after STII therapy [9][10][11][12][13][14][15] Strong HbA1c reduction often be achieved after dual-agent oral treatment 26,27 GLP-1RA leading to non-inferior HbA1c reductions than basal insulin; meanwhile, could lose weight 28,29 Potential mechanism Dedifferentiated β-cells redifferentiate to mature β-cells after insulin therapy 17,18 Lack of evidence…”

Section: Pros Consmentioning

confidence: 99%

“…For example, STII can quickly normalize glycemic control, improve β-cell function, restore first-phase insulin secretion, and even reduce glucagonemia in newly diagnosed T2DM, suggesting that it may provide unique capacity for modification of the natural process of diabetes. [9][10][11][12][13][14][15] The largest and most robust clinical trial of STII therapy enrolled 382 newly diagnosed people with T2DM at nine centers in China and randomized them to either insulin (short-term continuous subcutaneous insulin infusion [CSII] or multiple daily injections [MDI]) or oral anti-hyperglycemic therapy. 9 First-phase insulin secretion was increased in all three groups after 2 weeks of normoglycemia.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Short‐term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9%

Weng

2017

Journal of Diabetes

View full text Add to dashboard Cite

“…A wider survey of multiple studies using short-term intensive insulin treatment has indicated that approximately 40% of patients remain euglycemic and fee of antidiabetic pharmacotherapy at 24 months after the intensive insulin regimen (23, 24). …”

Section: β-Cell Dysfunction In Type 2 Diabetes Mellitusmentioning

confidence: 99%

The undoing and redoing of the diabetic β-cell

Wang

Liu

Jiménez-González

et al. 2017

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

A hallmark of type 2 diabetes (T2DM) is the reduction in functional β-cell mass, which is considered at least in part to result from an imbalance of β-cell renewal and apoptosis, with the latter being accelerated during metabolic stress. More recent studies, however, suggest that the loss of functional β-cell mass is not as much due to β-cell death but rather to de-differentiation of β-cells when these cells are exposed to metabolic stressors, opening the possibility to re-differentiate and restore functional β-cell mass by therapeutic intervention. In parallel, clinical observations suggest that temporary intensive insulin therapy in early diagnosed humans with T2DM, so as to “rest” endogenous β-cells, allows these patients to regain adequate insulin secretion and to maintain euglycemia for prolonged periods free of continued pharmacotherapy. Whether observations made in (mostly rodent) models of diabetes mellitus and in clinical trials are revealing identical mechanisms and therapeutic opportunities remains a tantalizing possibility. Our intention is for this review to serve as an overview of the field and commentary of this particularly exciting field of research.

show abstract

Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes

Abstract: Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.

Cited by 16 publications

References 37 publications

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Practical application of short-term intensive insulin therapy based on the concept of “treat to target” to reduce hypoglycaemia in routine clinical site

Short‐term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9%

The undoing and redoing of the diabetic β-cell

Contact Info

Product

Resources

About