t2d - very interesting...but, page-7

It is disappointing that there seems to be little room for real discussion on this forum. Far from being baseless, I include below both the MSB announcement which identifies a 0.3% reduction in HbA1c and a response to a British Medical Journal meatanalysis article which refers to "the 0.5% reduction in HbA1c that is generally accepted to be of clinical relevance". Sometimes it's a good idea to go beyond just what the MSB CEO has to say though even he was very subdued about these results.

The BMJ link is http://www.bmj.com/content/344/bmj.e486?tab=responses but I include the full response below.

MSB Announcement 4 December
MESOBLAST REPORTS POSITIVE TYPE 2 DIABETES TRIAL RESULTS

Melbourne, Australia and New York, USA; 4 December 2013: Regenerative medicine company Mesoblast Limited (ASX:MSB; USOTC:MBLTY) today announced top- line results from the Phase 2 trial of its proprietary Mesenchymal Precursor Cells
(MPCs) in subjects with type 2 diabetes. The results of the trial support the safety and tolerability of a single intravenous infusion of MPCs in type 2 diabetes. Additionally, there
was an improvement in glycemic control as evidenced by reduction in hemoglobin A1c
(HbA1c).

The Phase 2 randomized, single-blind, placebo-controlled, dose escalation trial was conducted across 18 sites in the United States. The trial evaluated the effects of a single intravenous infusion of 0.3, 1.0 or 2.0 million MPCs/kg or placebo over 12 weeks in 61 patients with a mean diabetes duration of 10 years.

Key positive findings were:

• The MPCs were safe and well tolerated with no treatment-related adverse events, meeting the trial's primary endpoint.
• Following a single intravenous MPC infusion, overall HbA1c levels were reduced
over the 12-week study period when compared to placebo.
• The highest dose showed the greatest overall reduction in HbA1c, with a peak decrease of 0.4% at 8 weeks compared with placebo (p<0.05), and a decrease of
0.3% at 12 weeks.
• In the less well-controlled subjects, as defined by a baseline HbA1c >8.0%, a
0.6% decrease in HbA1c was seen at 8 weeks in the high dose cohort compared with placebo.
• In those with baseline HbA1c <8%, a target of HbA1c <7% at week 12 was
achieved in 63% (5/8) of high-dose treated subjects compared with 0/7 placebo controls (p<0.05).

Mesoblast Chief Executive Silviu Itescu said: “We are very pleased and encouraged by these top-line results. In this phase 2 trial, a single injection of Mesoblast’s MPCs was well tolerated and showed evidence of improved glycemic control in type 2 diabetes, a chronic inflammatory disease affecting multiple organs.

“This is an important first step in developing an MPC-based immunomodulatory therapy for the treatment of type 2 diabetes and its complications.”

According to the World Health Organization, there are more than 347 million people worldwide with diabetes and the number is likely to more than double by 2030 without intervention. In the United States alone, according to the American Diabetes Association there were 18.8 million people suffering from type 2 diabetes in 2011. According to the United States Food and Drug Administration Guidance for Industry 2008, HbA1c is the primary endpoint of choice for glycemic control in subjects with type 2 diabetes.

















About Mesoblast
Mesoblast Limited (ASX: MSB; USOTC: MBLTY) is a world leader in the development of biologic products for the broad field of regenerative medicine. The Company’s proprietary technologies include its Mesenchymal Precursor Cell and culture-expanded Mesenchymal Stem Cell technology platforms, Dental Pulp Stem Cells and expanded
Hematopoietic Stem Cells. Mesoblast’s allogeneic or ‘off-the-shelf’ regenerative medicine
products are being developed for the treatment of conditions with significant unmet medical needs. The lead product candidates use its mesenchymal lineage cells in four
major and distinct areas - systemic inflammatory conditions, cardiovascular diseases,
orthopedic diseases of the spine, and oncology conditions. www.mesoblast.com

For further information, please contact:
Julie Meldrum
Corporate Communications
Mesoblast Limited
T: +61 (0) 3 9639 6036
E: [email protected]



BMJ Response
Title: SMBG is important along with Diabetes self-management education for management of type2 Diabetes as SMBG represents thus an important adjunct to HbA1C, because it probably differentiate fasting, pre-prandial, and postprandial hyperglycemia; detect glycemic excursions; identify hypoglycaemia; and may provide immediate feedback about the effect of food choices, physical exercise, and medication on glycemic control

The author of the article says that “It is widely agreed that for further evaluation of self monitoring of blood glucose(SMBG), the therapeutic interventions and efforts to promote behavioural change should be more tightly aligned to the results obtained from self monitoring, and targeted at those likely to benefit.

Early studies linking test results to specific drug and behavioural strategies have had promising results, although not achieving the 0.5% reduction in HbA1c that is generally accepted to be of clinical relevance. Smaller reductions of HbA1c level might be of importance from a public health perspective if achieved on a wide scale and at lower cost; however, costs of self monitoring remain high, even in low and middle income countries, with the costs of unsubsidised test strips varying from $0.35 in Australia to $3.11 in India.37 Until further studies can establish potential target groups and promising interventions to improve glycaemic control with self monitoring, our meta-analysis using individual patient data does not provide convincing evidence to support its routine use for people with non-insulin treated type 2 diabetes using the range of interventions employed within the included trials.”

It is fact that in India the cost of SMBG is very high; almost for strips Rs 600-700/= per month . The bulk of patients are not in financial capacity to spend for such high cost for daily check up at least thrice a day and to have food accordingly. Moreover, glucometer and strips result give many times does not reflect true glucose value except hypoglycaemia if occur.

It is however very good to detect hypoglycaemia in type 2 diabetics also. Diabetes care according this author is complex one and requires many vital issues to tackle, beyond only glycemic control. It requires a range of interventions and support to improve diabetes control and outcomes. If the author is not wrong, in 2009, an International Expert Committee, which included representatives from the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended the use of the HB A1C test to diagnose and monitoring diabetes, with a threshold of =6.5% , and ADA adopted this criterion in 2010 .

HbA1C reflects glycemic control for three months. This diagnostic test should be performed using a method that must be certified by the National Glyco-haemoglobin Standardization Program (NGSP) and NABL accredited Laboratories in West Bengal and must be standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. Point-of-care HbA1C assays, for which proficiency testing is probably mandated, are not sufficiently accurate at this time to use for diagnostic purposes in many laboratories of Kolkata metropolis even and not available in urban ,district or subdivisional and rural or state general hospitals of health care system in West Bengal india. So health care providers doctors have to depend on the established glucose criteria for the diagnosis of diabetes (FPG and 2-h PBG) and it remains valid as well for drug monitoring and control .

Just as there is less than 100% concordance between the FPG and 2-h PG tests, there is not perfect concordance between A1C and either glucose-based test. Analyses of National Health and Nutrition Examination Survey (NHANES) data also indicates that, assuming universal screening of the undiagnosed, the A1C cut point of =6.5% identifies one-third fewer cases of undiagnosed diabetes than a fasting glucose cut point of =126 mg/dL (7.0 mmol/L). However, in community practice, a large portion of the diabetic population remains still unaware of their condition in West Bengal. Thus, the lower sensitivity of Hb A1C at the designated cut point may well be offset by the test's greater practicality, and wider application of a more convenient test (A1C) may actually increase the number of diagnoses made. SMBG also may be carried out three or more times daily for patients who are using multiple insulin injections or insulin pump therapy or in Type 2 DM who are on OHA.

What is to be considered as glycemic control?

Assessment of glycemic control. Two primary techniques are available for health providers doctors and patients to assess the effectiveness of the management plan on glycemic control: patient self-monitoring of blood glucose (SMBG) or interstitial glucose, and Hb A1C which is not available in most places and cost 300 to 500 Rupees in Indian currency depending on laboratories where done.

Glucose monitoring Recommendations

• For patients using less-frequent insulin injections, noninsulin OHA therapies, or medical nutrition therapy (MNT) alone, SMBG may be useful as a guide towards management on consultation with doctor.
• To achieve postprandial glucose targets, postprandial SMBG may be appropriate.
• When prescribing SMBG, one must ensure that patients receive initial instruction in, and routine follow-up evaluation of, SMBG technique and their ability to use data to adjust therapy be insulin or OHA.
• Continuous glucose monitoring (CGM) in conjunction with intensive insulin regimens can be a useful tool to lower Hb A1C in selected adults (age =25 years) with type 1 diabetes( Insulin Dependent & MODY).
• Although the evidence for Hb A1C-lowering is less strong in children, teens, and younger adults, CGM may be helpful in these groups. Success correlates with adherence to ongoing use of the device.
• CGM may be a supplemental tool to SMBG in those with hypoglycaemia unawareness and/or frequent hypoglycaemic episodes.

Diabetes self-management education (DSME) is the difficult one but should be an ongoing process of facilitating the knowledge about diabetes, its complications, signs and symptoms of hypoglycaemia, benefit of daily exercise, care for foot , eye , infections , behavioural changes, skill, and ability necessary for diabetes self-care. This process incorporates the needs, goals, and life experiences of the persons with diabetes and is to be guided by evidence-based standard common and consequential SMBG information, motivation, and behavioural skills deficits which is usually present. The overall objectives of DSME are to support informed decision-making, self-care behaviours, problem-solving and active collaboration with the health care doctors team and to improve clinical outcomes, health status, and quality of life style. and patients with these gaps were less likely to test thus frequently. Clinical education focusing on relevant SMBG information, motivation to act, and behavioural skills for acting effectively may be thus a priority according to me. Real-time information provided by self-monitoring of blood glucose (SMBG) represents thus an important adjunct to A1C, because it probably differentiate fasting, preprandial, and postprandial hyperglycemia; detect glycemic excursions; identify hypoglycemia; and may provide immediate feedback about the effect of food choices, physical exercise, and medication on glycemic control.

The importance of SMBG is widely thus appreciated and may be recommended as a component of management in patients with type 1 or insulin-treated type 2 diabetes, or OHA treated type2 diabetes as well as in diabetic pregnancy, for both women with pregestational type 1 and gestational diabetes. Nevertheless, and of course HbA1C is best.