Effects of TCM on Beta-cell Function and Insulin Resistance in High Risk Chinese Individuals for T2D (TCM_PDiab_P01)
Effects of TCM on Beta-cell Function and Insulin Resistance in High Risk Chinese Individuals for T2D (TCM_PDiab_P01)
This study involves prediabetes volunteers who are at high risk of developing diabetes,
 including those with family history of diabetes, metabolic syndrome, fatty liver, polycystic
 ovary syndrome and history of gestational diabetes. They will take a 12-week course of
 formula: a) JinQi JiangTang Fang (JQJT) including Coptidis Rhizoma, Astragali Radix and
 Lonicerae Japonicae Flos, b) combined the ingredients of JQJT and Ophiopogonis Radix to make
 up a novel CM, Jin Mai Fang (JM); to evaluate the effectiveness of Chinese Medicine in
 preventing diabetes in a controlled setting in order to better understand their actions. They
 will be followed up for another 12 weeks after the treatment to evaluate the improvement in
 glucose tolerance of the formula.
In China, 10% of adults have diabetes and 30% of people have prediabetes. In Hong Kong, 2 in
 100 adults develop pre-diabetes every year and in 2014, 9% of adults have prediabetes. People
 with prediabetes have increased risk of cardiovascular disease and development of diabetes.
 Once developed, diabetes is associated with loss of 4-10 years of life depending on age of
 onset and 2-3 fold increased risk of cardiovascular, kidney and cancer events.

 Early detection and intervention of pre-diabetes will prevent progression from pre-diabetes
 to diabetes and reduce the risk of complications of diabetes. This focus on prevention
 concords with the concept of 'Zhi-Wei-Bing' in Chinese Medicine (CM). This is not only an
 important philosophy of CM but also a unique feature of Chinese culture. The 'Zhi-Wei-Bing'
 philosophy includes disease prevention, treatment, and rehabilitation.

 Insulin is secreted by the beta-cells of the pancreas which is the only hormone that can
 reduce blood glucose. People with diabetes have fewer pancreatic beta-cells than those
 without diabetes. Chinese Medicine contains multiple herbs which have been used in China for
 thousands of years. These herbal mixtures may alter the expression of these proteins which
 can lead to many biological effects including the possible benefits in reducing the risk of
 diabetes in high risk subjects.

 JinQi JiangTang Fang (JQJT) contains extracts from three herbs including Coptidis Rhizoma,
 Astragali Radix and Lonicerae Japonicae Flos and is one of the most popular formulae used by
 CMP for prevention of diabetes. The sustained blood glucose lowering effects of JQJT in male
 Zucker diabetic fatty rats. On multiomic analysis, the investigators observed concerted
 expression changes in a gene-gene network involving mRNA, miRNA and proteins implicated in
 fat metabolism and cell cycles.

 In this study, the investigators have combined the ingredients of JQJT and Ophiopogonis Radix
 (Maidong) to make up a novel CM formula, Jin Mai Fang (JM). According to TCM theory, Maidong
 nourishes the yin, promotes body fluid production, moistens the lung, eases the mind and
 clears away heart fire. The polysaccharide-rich extract of Maidong (0.06-240 mg/ml) has been
 shown to inhibit glucose absorption into the intestinal brush border membrane vesicles,
 reduce the activity of α-glucosidase and improve the activity of NIT-1 cells damaged by
 streptozotocin. These combined effects of inhibition of carbohydrate digestion and absorption
 and protection of the pancreatic islet cells provide a strong rationale for its use to
 prevent diabetes. The subjects will take a 12-week course of formula and they will be
 followed up for another 12 weeks after the treatment to evaluate the improvement in glucose
 tolerance of the formula.
Inclusion criteria

 -  Individuals aged ≥18 years-70 years

 -  BMI≥18 kg/m2

 -  Chinese ethnicity

 -  Individuals with pre-diabetes based on 75 gram oral glucose tolerance test (OGTT)
 defined as impaired fasting glycemia (fasting plasma glucose (FPG): ≥5.6-6.9 mmol/L)
 and/or impaired glucose tolerance (IGT) (2-h PG: ≥7.8-11.0 mmol/L) -

 -  Plus at least one risk factor(s) from the following list:

 -  2 components of the metabolic syndrome

 -  Triglyceride≥1.7 mmol/L

 -  BP≥130/80 mmHg

 -  HDL-C<1.3 mmol/L in women or <1.1 mmol/L in men

 -  Waist circumference≥80 cm in women or ≥90 cm in men

 -  Fatty liver

 -  Diagnosis by ultrasound scan and/or

 -  Diagnosis by fibroscan and/or

 -  Diagnosis by ALT>35 IU/L in men and >24 IU/L in women

 -  History of diabetes in first degree relatives

 -  History of gestational diabetes mellitus

 -  History of polycystic ovary syndrome

 Exclusion criteria

 -  Not willing to participate in this study or adhere to study procedures

 -  Significant medical history including but not limited to history of CVD, renal
 estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 and/or liver dysfunction
 (AST and/or ALT≥3 times upper limit of normal)

 -  History of drug abuse or excessive alcohol intake based on investigator judgment

 -  Dehydration, diarrhea or vomiting at the time of recruitment

 -  Subjects with severe infection, in perioperative period or with serious injury at the
 time of recruitment

 -  Subjects with blood haemoglobin outside the normal range (male: 13.5-17.5 g/dl and
 female: 12-15.5 g/dl)

 -  Subjects who have donated blood in the 3 months prior to the study and/or plan to
 donate blood during the study period

 -  Current use of dietary supplements or health products affecting glycose or galactose
 metabolism or body weight in previous 1 month before first dosing.

 -  Breast feeding, pregnant women or women with plans for pregnancy

 -  Any conditions considered unsuitable by the investigators

 -  Subjects with use of Warfarin

 -  Subjects with known G6PD deficiency or known history of herb-drug interactions

 -  Known history of diabetes mellitus and/or HbA1c >= 6.5%.

 -  Usage of glucose lowering drugs and/or weight loss drugs currently or within 1 month
 before first dosing

 -  Previous metabolic surgery

 -  Known history of thyroid disorders